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ENHERTU® (fam-trastuzumab deruxtecan-nxki) demonstrated a median progression-free survival of 14.3 months as 1st-line therapy in patients with HER2-mutant advanced non-small cell lung cancer in DESTINY-Lung04 Phase III trial

ENHERTU® (fam-trastuzumab deruxtecan-nxki) demonstrated a median progression-free survival of 14.3 months as 1st-line therapy in patients with HER2-mutant advanced non-small cell lung cancer in DESTINY-Lung04 Phase III trial

6-month improvement in median progression-free survival vs. pembrolizumab plus chemotherapy

AstraZeneca and Daiichi Sankyo’s ENHERTU is the first HER2-directed therapy to delay disease progression over standard of care in a Phase III trial in this setting

WILMINGTON, Del.–(BUSINESS WIRE)–
Positive results from the DESTINY-Lung04 Phase III trial showed AstraZeneca and Daiichi Sankyo’s ENHERTU® (fam-trastuzumab deruxtecan-nxki) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus global standard of care (platinum-pemetrexed doublet chemotherapy plus pembrolizumab) as a 1st-line treatment of patients with unresectable, locally advanced or metastatic HER2-mutant non-squamous non-small cell lung cancer (NSCLC).

Results were presented today during the Presidential Symposium at the IASLC 2026 World Conference on Lung Cancer (#WCLC26) hosted by the International Association for the Study of Lung Cancer in Seoul, South Korea (abstract #PL03.08).

In the primary endpoint of PFS, ENHERTU monotherapy significantly reduced the risk of disease progression or death by 37.0% versus pembrolizumab plus chemotherapy (hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.50-0.79; p<0.0001). Median PFS was 14.3 months with ENHERTU compared to 8.3 months for pembrolizumab plus chemotherapy as assessed by blinded independent central review (BICR). A favorable PFS trend was seen for ENHERTU across key subgroups, including the prespecified stratification factors of brain metastases, liver metastases, smoking status, HER2 mutation status (exon 19 or exon 20), and de novo or recurrent disease.

Objective response rate (ORR) with ENHERTU was 70.0% versus 44.5% with pembrolizumab plus chemotherapy. Median duration of response (DoR) for ENHERTU was 13.4 months and 9.7 months with pembrolizumab plus chemotherapy.

Julia Rotow, MD, Assistant Professor of Medicine, Dana-Farber Cancer Institute and lead investigator of the trial, said: “HER2-mutant non-small cell lung cancer is an aggressive disease with limited responses to current 1st-line standard of care, and many patients experience disease progression within a year of starting treatment. With seventy percent of patients responding and a median progression-free survival of 14.3 months, trastuzumab deruxtecan has the potential to become an important new 1st-line treatment option for these patients.”

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “DESTINY-Lung04 is the first Phase III trial to demonstrate superior progression-free survival versus the global 1st-line standard of care in patients with HER2-mutant advanced non-small cell lung cancer. These results add to the growing body of evidence supporting ENHERTU as an important treatment for patients with HER2 alterations and underscore its potential role at the time of metastatic diagnosis, when treatment has the greatest opportunity to improve outcomes.”

John Tsai, Global Head, R&D, Daiichi Sankyo, said: “ENHERTU was the first HER2-directed medicine and antibody drug conjugate approved for patients with HER2-mutant non-small cell lung cancer and has become a second-line standard-of-care treatment. The progression-free survival benefit of six months and strong response rates seen in DESTINY-Lung04 reinforce the importance of targeting HER2 directly in these patients and support the potential of ENHERTU in the 1st-line setting where delaying disease progression for as long as possible is a critical goal.”

Summary of results: DESTINY-Lung04i

Efficacy measure

ENHERTU

(5.4mg/kg; n=227)

Pembrolizumab plus chemotherapy

(n=227)

PFSii

Median PFS, (months) (95% CI)

14.3

(12.4-16.5)

8.3

(7.0-9.9)

Hazard ratio (95% CI)

HR 0.63 (0.50-0.79)

p-value

p<0.0001

ORRii,iii

ORR(%) (n)

(95% CI)iv

70.0% (159)

(63.6-75.9)

44.5% (101)

(37.9-51.2)

CR, % (n)

1.8% (4)

1.8% (4)

PR, % (n)

68.3% (155)

42.7% (97)

Median DOR, (months) (95% CI)

13.4

(10.4-17.2)

9.7

(7.0-11.1)

PFS2iii,v

Median PFS2, (months) (95% CI)

22.7

(20.3-26.3)

17.3

(15.6-21.8)

Hazard ratio (95% CI)

HR 0.80 (0.62-1.02)

OSvi

Median OS, (months) (95% CI)

29.3

(26.2-33.4)

33.1

(27.7-40.7)

Hazard ratio (95% CI)

HR 1.15 (0.88-1.52)

CI, confidence interval; CR, complete response; DOR, duration of response; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PR, partial response

 

i Analysis was based on a data cut-off (DCO) of 9 June 2026; median duration of follow-up was 21.6 in theENHERTU arm and 20.4 months in the pembrolizumab plus chemotherapy arm. At DCO, 40 patients (17.7%) remained in the ENHERTU arm and 10 patients (4.5%) in the pembrolizumab plus chemotherapy arm.

ii Assessed by BICR

iii Assessed by investigator

iv ORR is (CR + PR); includes unconfirmed responses

v PFS2 is defined as the time from randomization to second progression (earliest progression event following first subsequent therapy) or death

vi At DCO, overall data maturity for OS was 46.9% and no formal hypothesis testing was performed; formal hypothesis testing will be performed at the second interim analysis and final analysis

At the time of analysis, the overall survival (OS) data were 46.9% mature and no formal hypothesis testing was performed. While there was no observed benefit in OS, varied and imbalanced subsequent therapy patterns between arms may limit the interpretation of this result. Imbalances include greater use of HER2-directed therapies in the pembrolizumab plus chemotherapy arm versus the ENHERTU arm (48.0% vs 23.3%) and limited use of subsequent immunotherapy plus chemotherapy in the ENHERTU arm (23.8%).

The safety profile of ENHERTU observed in DESTINY-Lung04 was generally consistent with its known profile with no new safety concerns identified.

Despite longer treatment exposure in the ENHERTU arm (median 12.3 months versus 7.1 months), Grade 3 or higher treatment related adverse events (AEs) were comparable between ENHERTU and pembrolizumab plus chemotherapy (34.1% in the ENHERTU arm and 33.6% in the pembrolizumab plus chemotherapy arm). The most common Grade 3 or higher AE occurring in 5% or more of patients treated in both arms was neutropenia (occurring in 11.1% of patients in the ENHERTU arm and 14.1% in the pembrolizumab plus chemotherapy arm). Interstitial lung disease (ILD) or pneumonitis events occurred in 20.8% of patients treated with ENHERTU as determined by an independent adjudication committee. The majority of ILD or pneumonitis events were low Grade (Grade 1 [n=7; 3.1%] or Grade 2 [n=30; 13.3%]). There were five Grade 3 (2.2%), one Grade 4 (0.4%) and four Grade 5 (1.8%) ILD events in the ENHERTU arm.

ENHERTU is approved to treat patients with previously treated metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, and to treat patients with HER2-positive solid tumors, including HER2-overexpressing metastatic NSCLC, who have received prior treatment and who have no satisfactory treatment options.

ENHERTU is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo.

Enhertu U.S. Indications and Important Safety Information

Indications

ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for:

  • HER2-Positive Early Breast Cancer

    – As neoadjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) Stage II or III breast cancer, as determined by an FDA-authorized test followed by a taxane, trastuzumab, and pertuzumab (THP)

    – As adjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) breast cancer who have residual invasive disease following neoadjuvant trastuzumab (with or without pertuzumab) and taxane-based treatment

  • HER2-Positive Metastatic Breast Cancer

    – In combination with pertuzumab as first-line treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-authorized test

    – As monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or, in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy

  • HER2-Low and HER2-Ultralow Metastatic Breast Cancer

    – As monotherapy for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA-authorized test, that has progressed on one or more endocrine therapies in the metastatic setting

    – As monotherapy for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-authorized test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy

  • HER2-Mutant Unresectable or Metastatic Non-Small Cell Lung Cancer (NSCLC)

    – As monotherapy for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-authorized test, and who have received a prior systemic therapy

    This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

  • HER2-Positive Locally Advanced or Metastatic Gastric Cancer

    – As monotherapy for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH positive) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen

  • HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors

    – As monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options

    This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Important Safety Information

WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

  • Interstitial lung disease (ILD) and pneumonitis, including severe, life-threatening, and fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms.
  • Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception.

Contraindications

None.

Warnings and Precautions

Interstitial Lung Disease / Pneumonitis

Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose 1 level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks. In the adjuvant HER2+ breast cancer setting, if drug-induced ILD is suspected, rule out radiotherapy-related pneumonitis. If only radiotherapy-related pneumonitis is suspected, consider interruption of ENHERTU for Grade 2 and permanently discontinue ENHERTU for Grade ≥3.

HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)

ENHERTU as Monotherapy

In patients treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. Median time to first onset was 5.5 months (range: 0.9 to 31.5). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.9% of patients treated with ENHERTU.

ENHERTU in Combination with Pertuzumab

In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), ILD occurred in 12% of patients. Median time to first onset was 8.0 months (range: 0.6 to 33.8). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.5% of patients treated with ENHERTU in combination with pertuzumab.

ENHERTU followed by THP

In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, ILD occurred in 4.4% of patients. Median time to first onset was 2.7 months (range: 1.1 to 6.0). Fatal outcomes due to ILD and/or pneumonitis occurred in 1 patient (0.3%) treated with ENHERTU followed by THP.

HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)

In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21).

Neutropenia

Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then reduce dose by 1 level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3º C or a sustained temperature of ≥38º C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by 1 level.

HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)

ENHERTU as Monotherapy

In patients treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients. Nineteen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 939). Febrile neutropenia was reported in 1% of patients.

ENHERTU in Combination with Pertuzumab

In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), decreased neutrophil count occurred in 79% of patients. Median time to first onset was 22 days (range: 5 to 994). Twenty-nine percent had Grade 3 or 4 decreased neutrophil count. Febrile neutropenia was reported in 2.6% of patients.

ENHERTU followed by THP

In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, a decrease in neutrophil count was reported in 58% of patients. Seventeen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 42 days (range: 11 to 165). Febrile neutropenia was reported in 0.9% of patients.

HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)

In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients.

Left Ventricular Dysfunction

Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular dysfunction (LVD) has been observed with anti-HER2 therapies, including ENHERTU. Assess left ventricular ejection fraction (LVEF) prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVD through treatment interruption. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.

HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)

ENHERTU as Monotherapy

In patients treated with ENHERTU 5.4 mg/kg, LVD was reported in 4.6% of patients, of which 0.6% were Grade 3 or 4.

ENHERTU in Combination with Pertuzumab

In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), LVEF decrease was reported in 11% of patients, of which 2.1% were Grade 3 or 4.

ENHERTU followed by THP

In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, LVD was reported in 1.3% of patients, of which 0.3% were Grade 3.

HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)

In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF.

Embryo-Fetal Toxicity

ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose of ENHERTU.

Additional Dose Modifications

Thrombocytopenia

For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then reduce dose by 1 level.

Adverse Reactions

HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)

ENHERTU as Monotherapy

The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 2233 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast02, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Breast06, DESTINY-Lung01, DESTINY-Lung02, DESTINY-CRC02, and DESTINY-PanTumor02. Among these patients, 67% were exposed for >6 months and 39% were exposed for >1 year. In this pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (73%), nausea (72%), decreased hemoglobin (67%), decreased neutrophil count (65%), decreased lymphocyte count (60%), fatigue (55%), decreased platelet count (48%), increased aspartate aminotransferase (46%), increased alanine aminotransferase (43%), increased blood alkaline phosphatase (39%), vomiting (38%), alopecia (37%), constipation (32%), decreased blood potassium (32%), decreased appetite (31%), diarrhea (30%), and musculoskeletal pain (24%).

ENHERTU in Combination with Pertuzumab

The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg in combination with pertuzumab intravenously every 3 weeks in 431 patients in DESTINY-Breast07 (n=50), and DESTINY-Breast09 (n=381). Among these patients, 86% were exposed for >6 months and 73% were exposed for >1 year. In this pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (86%), decreased hemoglobin (80%), decreased neutrophil count (79%), nausea (74%), increased alanine aminotransferase (65%), diarrhea (64%), increased aspartate aminotransferase (63%), decreased lymphocyte count (61%), decreased platelet count (55%), increased blood alkaline phosphatase (54%), decreased blood potassium (54%), fatigue (53%), alopecia (48%), vomiting (46%), upper respiratory tract infection (32%), constipation (31%), decreased appetite (31%), decreased weight (28%), musculoskeletal pain (23%), increased blood bilirubin (23%), and abdominal pain (22%).

HER2-Positive Early Breast Cancer

DESTINY-Breast11

The safety of ENHERTU followed by THP was evaluated in 320 patients with HER2-positive (IHC 3+ or ISH+) early breast cancer who received at least 1 dose of ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11. ENHERTU was administered by intravenous infusion once every three weeks for 4 cycles followed by THP for 4 cycles. The median duration of treatment was 5.6 months (range: 0.7 to 9.1) for patients who received ENHERTU followed by THP.

Serious adverse reactions occurred in 11% of patients receiving ENHERTU followed by THP, including COVID-19 (0.9%) and ILD/pneumonitis (0.6%). Fatal adverse reactions occurred in 0.6% of patients, including ILD/pneumonitis and death not otherwise specified (1 patient each).

In patients treated with ENHERTU followed by THP, the permanent discontinuation of ENHERTU due to adverse reactions occurred in 1.3%, of which ILD/pneumonitis accounted for 0.6%. Dose interruptions of ENHERTU due to adverse reactions occurred in 11% of patients. The most frequent adverse reactions (>2%) associated with dose interruption were decreased neutrophil count and COVID-19. Dose reductions of ENHERTU occurred in 2.5% of patients treated with ENHERTU.

The most common (≥20%) adverse reactions in patients treated with ENHERTU followed by THP, including laboratory abnormalities, were decreased hemoglobin (83%), increased alanine aminotransferase (79%), increased aspartate aminotransferase (74%), decreased white blood cell count (67%), nausea (65%), peripheral neuropathy (59%), diarrhea (59%), decreased neutrophil count (58%), alopecia (48%), fatigue (41%), decreased lymphocyte count (40%), rash (31%), musculoskeletal pain (30%), decreased blood potassium (29%), constipation (29%), vomiting (29%), stomatitis (23%), and decreased appetite (20%).

DESTINY-Breast05

The safety of ENHERTU was evaluated in 806 patients with HER2-positive breast cancer with residual invasive disease following neoadjuvant HER2-targeted therapy who then received at least one dose of ENHERTU 5.4 mg/kg. ENHERTU was administered by intravenous infusion once every three weeks for 14 cycles. The median duration of treatment was 10 months (range: 0.7 to 16) for patients who received ENHERTU.

Serious adverse reactions occurred in 17% of patients receiving ENHERTU. Serious adverse reactions in ≥1% of patients who received ENHERTU were ILD/pneumonitis, radiation pneumonitis, pneumonia, and platelet count decreased. Fatal adverse reactions occurred in 0.4% of patients including ILD/pneumonitis (2 patients) and respiratory tract infection (1 patient).

Permanent discontinuation of ENHERTU due to an adverse reaction occurred in 18% of patients. The adverse reaction which resulted in permanent discontinuation of ENHERTU >2% included ILD/pneumonitis. Dose interruptions of ENHERTU due to an adverse reaction occurred in 50% of patients. Adverse reactions which required dosage interruptions in >2% included radiation pneumonitis, neutrophil count decreased, COVID-19, white blood cell count decreased, ILD/pneumonitis, platelet count decreased, upper respiratory tract infection, fatigue, cough, and pyrexia. Dose reductions of ENHERTU due to an adverse reaction occurred in 26% of patients. Adverse reactions which required dose reductions in >2% of patients included nausea, fatigue, platelet count decreased, ILD/pneumonitis, and neutrophil count decreased.

The most common (≥20%) adverse reactions, including laboratory abnormalities, in patients receiving ENHERTU were decreased white blood cell count (80%), decreased lymphocyte count (72%), decreased neutrophil count (72%), nausea (71%), decreased hemoglobin (61%), increased aspartate aminotransferase (60%), fatigue (54%), increased alanine aminotransferase (53%), decreased platelet count (46%), increased blood alkaline phosphatase (39%), constipation (32%), vomiting (31%), decreased blood potassium (27%), diarrhea (23%), musculoskeletal pain (23%), and decreased appetite (20%).

ILD was reported in 17% of patients receiving ENHERTU, which included COVID-19 pneumonia, interstitial lung disease, lung opacity, organizing pneumonia, pneumocystis jirovecii pneumonia, pneumonia, and pneumonitis which was adjudicated as ILD (irrespective of causality). Adjudicated drug-related ILD for ENHERTU was 10% for all Grades and 0.9% for Grades 3 or 4.

HER2-Positive Metastatic Breast Cancer

DESTINY-Breast09

The safety of ENHERTU 5.4 mg/kg in combination with pertuzumab was evaluated in DESTINY-Breast09, a randomized, three-arm, multicenter study including 763 patients with HER2-positive (IHC 3+ or ISH+) unresectable or metastatic breast cancer. Three hundred eighty-one patients received ENHERTU in combination with pertuzumab and 382 patients received THP (taxane [docetaxel or paclitaxel], trastuzumab, and pertuzumab). Among patients who received ENHERTU in combination with pertuzumab, the median duration of treatment was 22 months (range: 0.3 months to 44.5 months).

Serious adverse reactions occurred in 27% of patients receiving ENHERTU in combination with pertuzumab. Serious adverse reactions in >1% of patients were diarrhea, pneumonia, febrile neutropenia, hypokalemia, vomiting, ILD, pulmonary embolism, and sepsis. Fatalities due to adverse reactions occurred in 3.4% of patients including pneumonia (n=3), ILD (n=2), sepsis (n=2), pulmonary embolism, septic shock, acute kidney injury, dyspnea, febrile neutropenia, and intestinal ischemia (1 patient each).

ENHERTU was discontinued for adverse reactions in 21% of patients. The most frequent adverse reaction (>2%) associated with permanent discontinuation was ILD/pneumonitis (6%). Dose interruptions due to adverse reactions occurred in 69% of patients. The most frequent adverse reactions (>2%) associated with dose interruption were COVID-19, neutropenia, upper respiratory tract infection, fatigue, anemia, hypokalemia, ILD/pneumonitis, thrombocytopenia, pneumonia, diarrhea, transaminase increased, leukopenia, cough, pyrexia, decreased appetite, and blood bilirubin increased. Dose reductions occurred in 46% of patients treated with ENHERTU in combination with pertuzumab. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, neutropenia, nausea, diarrhea, ILD/pneumonitis, thrombocytopenia, vomiting, transaminases increased, decreased weight, febrile neutropenia, and hypokalemia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (87%), decreased hemoglobin (80%), decreased neutrophil count (78%), nausea (75%), increased alanine aminotransferase (66%), diarrhea (64%), increased aspartate aminotransferase (62%), decreased lymphocyte count (62%), decreased platelet count (56%), increased blood alkaline phosphatase (55%), decreased blood potassium (54%), fatigue (53%), alopecia (48%), vomiting (46%), upper respiratory tract infection (33%), constipation (33%), decreased appetite (32%), decreased weight (30%), COVID-19 (28%), musculoskeletal pain (24%), increased blood bilirubin (23%), and abdominal pain (23%).

DESTINY-Breast03

The safety of ENHERTU was evaluated in 257 patients with unresectable or metastatic HER2-positive breast cancer who received at least 1 dose of ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast03. The median duration of treatment was 14 months (range: 0.7 to 30) for patients who received ENHERTU.

Serious adverse reactions occurred in 19% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were vomiting, ILD, pneumonia, pyrexia, and urinary tract infection. Fatalities due to adverse reactions occurred in 0.8% of patients including COVID-19 and sudden death (1 patient each).

ENHERTU was permanently discontinued in 14% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 44% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, leukopenia, anemia, thrombocytopenia, pneumonia, nausea, fatigue, and ILD/pneumonitis. Dose reductions occurred in 21% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, neutropenia, and fatigue.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (74%), decreased neutrophil count (70%), increased aspartate aminotransferase (67%), decreased hemoglobin (64%), decreased lymphocyte count (55%), increased alanine aminotransferase (53%), decreased platelet count (52%), fatigue (49%), vomiting (49%), increased blood alkaline phosphatase (49%), alopecia (37%), decreased blood potassium (35%), constipation (34%), musculoskeletal pain (31%), diarrhea (29%), decreased appetite (29%), headache (22%), respiratory infection (22%), abdominal pain (21%), increased blood bilirubin (20%), and stomatitis (20%).

HER2-Low and HER2-Ultralow Metastatic Breast Cancer

DESTINY-Breast06

The safety of ENHERTU was evaluated in 434 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast06. The median duration of treatment was 11 months (range: 0.4 to 39.6) for patients who received ENHERTU.

Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, COVID-19, febrile neutropenia, and hypokalemia. Fatalities due to adverse reactions occurred in 2.8% of patients including ILD (0.7%); sepsis (0.5%); and COVID-19 pneumonia, bacterial meningoencephalitis, neutropenic sepsis, peritonitis, cerebrovascular accident, general physical health deterioration (0.2% each).

ENHERTU was permanently discontinued in 14% of patients. The most frequent adverse reaction (>2%) associated with permanent discontinuation was ILD/pneumonitis. Dose interruptions due to adverse reactions occurred in 48% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were COVID-19, decreased neutrophil count, anemia, pyrexia, pneumonia, decreased white blood cell count, and ILD. Dose reductions occurred in 25% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, fatigue, decreased platelet count, and decreased neutrophil count.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (86%), decreased neutrophil count (75%), nausea (70%), decreased hemoglobin (69%), decreased lymphocyte count (66%), fatigue (53%), decreased platelet count (48%), alopecia (48%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (43%), increased aspartate aminotransferase (41%), decreased blood potassium (35%), diarrhea (34%), vomiting (34%), constipation (32%), decreased appetite (26%), COVID-19 (26%), and musculoskeletal pain (24%).

DESTINY-Breast04

The safety of ENHERTU was evaluated in 371 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast04. The median duration of treatment was 8 months (range: 0.2 to 33) for patients who received ENHERTU.

Serious adverse reactions occurred in 28% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, pneumonia, dyspnea, musculoskeletal pain, sepsis, anemia, febrile neutropenia, hypercalcemia, nausea, pyrexia, and vomiting. Fatalities due to adverse reactions occurred in 4% of patients including ILD/pneumonitis (3 patients); sepsis (2 patients); and ischemic colitis, disseminated intravascular coagulation, dyspnea, febrile neutropenia, general physical health deterioration, pleural effusion, and respiratory failure (1 patient each).

ENHERTU was permanently discontinued in 16% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 39% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, fatigue, anemia, leukopenia, COVID-19, ILD/pneumonitis, increased transaminases, and hyperbilirubinemia. Dose reductions occurred in 23% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, thrombocytopenia, and neutropenia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (70%), decreased hemoglobin (64%), decreased neutrophil count (64%), decreased lymphocyte count (55%), fatigue (54%), decreased platelet count (44%), alopecia (40%), vomiting (40%), increased aspartate aminotransferase (38%), increased alanine aminotransferase (36%), constipation (34%), increased blood alkaline phosphatase (34%), decreased appetite (32%), musculoskeletal pain (32%), diarrhea (27%), and decreased blood potassium (25%).

HER2-Mutant Unresectable or Metastatic NSCLC (5.4 mg/kg)

DESTINY-Lung02 evaluated 2 dose levels (5.4 mg/kg [n=101] and 6.4 mg/kg [n=50]); however, only the results for the recommended dose of 5.4 mg/kg intravenously every 3 weeks are described below due to increased toxicity observed with the higher dose in patients with NSCLC, including ILD/pneumonitis.

The safety of ENHERTU was evaluated in 101 patients with HER2-mutant unresectable or metastatic NSCLC who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks until disease progression or unacceptable toxicity in DESTINY‑Lung02. The median duration of treatment was 8 months (range: 0.7 to 28) for patients who received ENHERTU.

Serious adverse reactions occurred in 40% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, pleural effusion, thrombocytopenia, dyspnea, nausea, pneumonia, vomiting, myocarditis, pulmonary embolism, and increased troponin I. Fatalities due to adverse reactions occurred in 3% of patients including ILD/pneumonitis, cerebrovascular accident, and pneumococcal sepsis (1 patient each).

ENHERTU was permanently discontinued in 17% of patients. Adverse reactions which resulted in permanent discontinuation of ENHERTU were ILD/pneumonitis, pneumonia, blood bilirubin increased, hypokalemia, metastases to meninges, and myocarditis. Dose interruptions of ENHERTU due to adverse reactions occurred in 50% of patients. Adverse reactions which required dose interruption (>2%) included neutropenia, COVID-19, ILD/pneumonitis, fatigue, anemia, and pneumonia. Dose reductions due to an adverse reaction occurred in 20% of patients. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, fatigue, and decreased appetite.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (68%), nausea (67%), decreased white blood cell count (66%), decreased neutrophil count (59%), decreased lymphocyte count (56%), increased aspartate aminotransferase (51%), decreased albumin (50%), decreased platelet count (49%), fatigue (48%), increased alanine aminotransferase (41%), decreased appetite (41%), constipation (38%), increased alkaline phosphatase (37%), vomiting (32%), decreased blood potassium (29%), diarrhea (24%), alopecia (22%), and musculoskeletal pain (21%).

HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)

The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01. Patients intravenously received at least 1 dose of either ENHERTU (N=125) 6.4 mg/kg every 3 weeks or either irinotecan (N=55) 150 mg/m2 biweekly or paclitaxel (N=7) 80 mg/m2 weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) for patients who received ENHERTU.

Serious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients who received ENHERTU were decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in 1 patient each (0.8%).

ENHERTU was permanently discontinued in 15% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 62% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and decreased blood potassium. Dose reductions occurred in 32% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (75%), decreased white blood cell count (74%), decreased neutrophil count (72%), decreased lymphocyte count (70%), decreased platelet count (68%), nausea (63%), decreased appetite (60%), increased aspartate aminotransferase (58%), fatigue (55%), increased blood alkaline phosphatase (54%), increased alanine aminotransferase (47%), diarrhea (32%), decreased blood potassium (30%), vomiting (26%), constipation (24%), increased blood bilirubin (24%), pyrexia (24%), and alopecia (22%).

HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors

The safety of ENHERTU was evaluated in 347 adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast01, DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02. The median duration of treatment was 8.3 months (range 0.7 to 30.2).

Serious adverse reactions occurred in 34% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were sepsis, pneumonia, vomiting, urinary tract infection, abdominal pain, nausea, pneumonitis, pleural effusion, hemorrhage, COVID-19, fatigue, acute kidney injury, anemia, cellulitis, and dyspnea. Fatalities due to adverse reactions occurred in 6.3% of patients including ILD/pneumonitis (2.3%), cardiac arrest (0.6%), COVID-19 (0.6%), and sepsis (0.6%). The following events occurred in 1 patient each (0.3%): acute kidney injury, cerebrovascular accident, general physical health deterioration, pneumonia, and hemorrhagic shock.

ENHERTU was permanently discontinued in 15% of patients, of which ILD/pneumonitis accounted for 10%. Dose interruptions due to adverse reactions occurred in 48% of patients. The most frequent adverse reactions (>2%) associated with dose interruption were decreased neutrophil count, anemia, COVID-19, fatigue, decreased white blood cell count, and ILD/pneumonitis. Dose reductions occurred in 27% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, decreased neutrophil count, ILD/pneumonitis, and diarrhea.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (75%), nausea (69%), decreased hemoglobin (67%), decreased neutrophil count (66%), fatigue (59%), decreased lymphocyte count (58%), decreased platelet count (51%), increased aspartate aminotransferase (45%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (36%), vomiting (35%), decreased appetite (34%), alopecia (34%), diarrhea (31%), decreased blood potassium (29%), constipation (28%), decreased sodium (22%), stomatitis (20%), and upper respiratory tract infection (20%).

Use in Specific Populations

  • Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months after the last dose of ENHERTU.
  • Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose.
  • Females and Males of Reproductive Potential:Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for 7 months after the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose. Infertility: ENHERTU may impair male reproductive function and fertility.
  • Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.
  • Geriatric Use: ENHERTU as Monotherapy:Of the 2233 patients treated with ENHERTU 5.4 mg/kg, 28% were ≥65 years and 6% were ≥75 years. No overall differences in efficacy within clinical studies were observed between patients ≥65 years compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (56%) as compared to younger patients (49%). Of the 125 patients with HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were ≥65 years and 14% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. ENHERTU in Combination with Pertuzumab:In patients with HER2-positive unresectable or metastatic breast cancer treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), 17% were ≥65 years and 3% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years compared to younger patients. ENHERTU followed by THP: Of the 320 patients with HER2-positive early breast cancer treated with ENHERTU 5.4 mg/kg followed by THP, 12% were ≥65 years and 1.6% were ≥75 years. No overall differences in efficacy were observed between patients ≥65 years compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients ≥65 years (38%) as compared to younger patients (30%).
  • Renal Impairment: A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Monitor patients with moderate renal impairment more frequently. The recommended dosage of ENHERTU has not been established for patients with severe renal impairment (CLcr <30 mL/min).
  • Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, monitor for increased adverse reactions related to the topoisomerase inhibitor, DXd. The recommended dosage of ENHERTU has not been established for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST).

To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.

Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

Notes

HER2-mutant NSCLC

Lung cancer is the most commonly diagnosed cancer globally and remains the leading cause of cancer-related death.1 In 2024, approximately 2.6 million new lung cancer cases were reported worldwide, with an estimated 1.8 million deaths.1 NSCLC is the most common type of lung cancer, accounting for approximately 85% of cases.2 Prognosis is particularly poor for patients with metastatic NSCLC as only approximately 10% will live beyond five years after diagnosis.3-5

HER2 is a tyrosine kinase receptor protein involved in cell growth and differentiation and expressed on the surface of multiple tumor types. HER2 mutations have been identified in NSCLC as distinct molecular targets and have been reported in approximately 2-4% of patients with non-squamous NSCLC.6-9 These HER2 mutations are predominantly seen in younger women and people with no smoking history and have been independently associated with cancer cell growth and poor prognosis, with an increased incidence of brain metastases.6, 10-14

The global standard of care in the 1st-line metastatic setting of patients with HER2-mutant NSCLC is a combination of immunotherapy and doublet platinum-based chemotherapy.15-17 However, many patients do not respond to 1st-line treatment and experience disease progression, underscoring the need for additional treatment options.18

DESTINY-Lung04

DESTINY-Lung04 is a global, randomized, open-label, Phase III trial evaluating the efficacy and safety of ENHERTU (5.4mg/kg) compared to standard of care (platinum-pemetrexed doublet chemotherapy in combination with pembrolizumab) in patients with unresectable, locally advanced or metastatic, non-squamous NSCLC harboring a HER2 exon 19 or 20 mutation.

Patients were randomized 1:1 to receive either ENHERTU or standard of care. Randomization was stratified by smoking history and presence or history of brain metastasis. The primary endpoint of DESTINY-Lung04 is PFS as assessed by BICR. Secondary endpoints include ORR and DOR assessed by BICR and investigator, PFS2 by investigator, OS, pharmacokinetics and safety.

DESTINY-Lung04 enrolled 454 patients across multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.

ENHERTU

ENHERTU is a HER2-directed ADC. Designed using the proprietary DXd ADC Technology of Daiichi Sankyo, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

ENHERTU (5.4mg/kg) followed by THP is approved in the US, China, India, Singapore, Brazil and Taiwan as a neoadjuvant treatment for adult patients with HER2-positive (IHC 3+ or ISH+) Stage 2 or Stage 3 breast cancer based on the results from the DESTINY-Breast11 trial. Continued approval in China for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ENHERTU (5.4mg/kg) is approved in the US, Brazil, India and Canada for the adjuvant treatment of adult patients with HER2-positive breast cancer who have residual invasive disease following neoadjuvant trastuzumab (with or without pertuzumab) and taxane-based treatment based on the DESTINY-Breast05 trial.

ENHERTU (5.4mg/kg) in combination with pertuzumab is approved in more than 40 countries worldwide as a 1st-line treatment for adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, as determined by a locally or regionally approved test, based on the results from the DESTINY-Breast09 trial.

ENHERTU (5.4mg/kg) is approved in more than 100 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

ENHERTU (5.4mg/kg) is approved in more than 75 countries worldwide for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial.

ENHERTU (5.4mg/kg) is approved in more than 100 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

ENHERTU (5.4mg/kg) is approved in more than 80 countries worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ENHERTU (6.4mg/kg) is approved in more than 90 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric04 trials.

ENHERTU (5.4mg/kg) is approved in more than 45 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01, DESTINY-CRC02 and/or HERALD trials. Continued approval in the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ENHERTU clinical development program

A comprehensive global clinical development program is underway evaluating the efficacy and safety of ENHERTU as a monotherapy or in combination or sequentially with other cancer medicines across multiple HER2-targetable cancers.

Daiichi Sankyo collaboration

AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and datopotamab deruxtecan-dlnk in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and datopotamab deruxtecan-dlnk.

AstraZeneca in lung cancer

AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most.

The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including osimertinib and gefitinib; durvalumab and tremelimumab; ENHERTU and datopotamab deruxtecan-dlnk in collaboration with Daiichi Sankyo; savolitinibin collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.

AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment.

AstraZeneca in oncology

AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 125 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca.

References

  1. World Health Organization. Lung Cancer Fact Sheet. Available at: https://gco.iarc.who.int/today/en/fact-sheets-cancers/15/trachea-bronchus-and-lung. Accessed September 2026.

  2. Leiter A, et al. The global burden of lung cancer: current status and future trends. Nat Rev Clin Oncol. 2023;20(9):624-639.

  3. Tamura T, et al. Specific organ metastases and survival in metastatic non-small cell lung cancer. Mol Clin Oncol. 2015;3(1):217-221.

  4. Goldstraw P, et al. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. JThorac Oncol. 2016;11(1):39-51.

  5. Siegel RL, et al. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71(1):7-33.

  6. Mazieres J, et al. Lung Cancer That Harbors an HER2 Mutation: Epidemiologic Characteristics and Therapeutic Perspectives. J Clin Oncol. 2013;31(16):1997-2003.

  7. cBioPortal for Cancer Genomics. Available at: https://www.cbioportal.org/. Accessed September 2026.

  8. Yoshizawa A, et al. HER2 Status In Lung Adenocarcinoma: A Comparison Of Immunohistochemistry, Fluorescence In Situ Hybridization (FISH), Dual-ISH, and Gene Mutations. Lung Cancer. 2014;85(3):373-378.

  9. Li BT, et al. HER2 Amplification and HER2 Mutation Are Distinct Molecular Targets in Lung Cancers. J Thorac Oncol. 2016;11(3):414-9.

  10. Liu S, et al. Targeting HER2 Aberrations in Non–Small Cell Lung Cancer with Osimertinib. Clin Cancer Res. 2018;24(11):2594-2604.

  11. Stephens P, et al. Lung cancer: intragenic ERBB2 kinase mutations in tumours. Nature. 2004;431:525-6.

  12. Arcila ME, et al. Prevalence, Clinicopathologic Associations, and Molecular Spectrum of ERBB2 (HER2) Tyrosine Kinase Mutations in Lung Adenocarcinomas. Clin Cancer Res. 2012;18:4910-8.

  13. Pillai RN, et al. HER2 mutations in lung adenocarcinomas: A report from the Lung Cancer Mutation Consortium. Cancer. 2017;123:4099-105.

  14. Offin M, et al. Frequency and outcomes of brain metastases in patients with HER2-mutant lung cancers. Cancer. 2019;125:4380-7.

  15. Hendriks LE, et al. Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(4):339-357.

  16. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Version 5.2026. March 13, 2026. Available at: http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed September 2026.

  17. Man J, et al. Response Rate and Survival at Key Timepoints With PD-1 Blockade vs Chemotherapy in PD-L1 Subgroups: Meta-Analysis of Metastatic NSCLC Trials. JNCI Cancer Spectr. 2021;5(3):pkab012.

  18. Saalfeld FC, et al. Efficacy of Immune Checkpoint Inhibitors Alone or in Combination With Chemotherapy in NSCLC Harboring ERBB2 Mutations. J Thorac Oncol. 2021;16:1952–1958.

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TAGRISSO® (osimertinib) demonstrated unprecedented eight-year landmark survival in early-stage EGFR-mutated lung cancer in ADAURA Phase III trial

TAGRISSO® (osimertinib) demonstrated unprecedented eight-year landmark survival in early-stage EGFR-mutated lung cancer in ADAURA Phase III trial

Longest survival data ever reported in a global Phase III trial in this setting

New data reinforce TAGRISSO as the standard of care and backbone therapy in EGFRm lung cancer across stages

WILMINGTON, Del.–(BUSINESS WIRE)–
Updated exploratory results from the ADAURA Phase III trial showed AstraZeneca’s TAGRISSO® (osimertinib) demonstrated a sustained, clinically meaningful overall survival (OS) benefit at eight years compared to placebo in the adjuvant treatment of patients with early-stage (IB, II and IIIA) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after complete tumor resection with curative intent.

These results were presented today during the Presidential Symposium at the IASLC 2026 World Conference on Lung Cancer (#WCLC26) hosted by the International Association for the Study of Lung Cancer in Seoul, Republic of Korea (Abstract PL03.01). These data were also simultaneously published in the Journal of Thoracic Oncology.

At eight years of follow-up, results showed that TAGRISSO continued to show an OS benefit, reducing the risk of death compared to placebo by 47% in the primary population (Stages II-IIIA) (based on a hazard ratio [HR] of 0.53; 95% confidence interval [CI] 0.38-0.75). In the overall trial population (Stages IB-IIIA), TAGRISSO reduced the risk of death compared to placebo by 48% (HR 0.52; 95% CI 0.39-0.71). An estimated 74% of patients treated with TAGRISSO were alive at eight years versus 58% of those treated with placebo in the primary population. In the overall trial population, an estimated 79% of patients treated with TAGRISSO were alive at eight years versus 64% of those treated with placebo. Consistent with the planned final analysis, OS benefit with TAGRISSO versus placebo was observed across all predefined subgroups.

Roy S. Herbst, MD, PhD, Director at Dartmouth Cancer Center, and principal investigator in the ADAURA Phase III trial, said: “These ADAURA findings show patients continue to experience meaningful, long-term benefit following early intervention with adjuvant osimertinib, with a 16 percent point improvement in overall survival at eight years versus placebo. This is especially impressive given high rates of crossover to osimertinib following disease recurrence. This durable overall survival benefit reinforces the importance of prioritizing EGFR testing at diagnosis so as many patients as possible can benefit from this transformative therapy.”

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “ADAURA continues to set new benchmarks in early-stage EGFR-mutated lung cancer, with nearly 80 percent of patients treated with adjuvant TAGRISSO alive at eight years. These results underscore the importance of treating early and reinforce TAGRISSO as the adjuvant standard of care and backbone therapy across stages of the disease.”

Summary of updated OS results: ADAURAi,ii

 

TAGRISSO

Placebo

Stages II-IIIA (primary population)

(n=233)

(n=237)

Median duration of follow-up, in months

92

68.5

OS HR (95% CI)

0.53 (0.38, 0.75)

OS rate at 96 months (95% CI), %

74 (67, 80)

58 (50, 65)

Stage IB-IIIA (overall population)

(n=339)

(n=343)

Median duration of follow-up, in months

93.3

79.6

OS HR (95% CI)

0.52 (0.39, 0.71)

OS rate at 96 months (95% CI), %

79 (74, 83)

64 (58, 70)

i The updated analysis data cut-off (DCO) date was May 4, 2026.

ii This exploratory long-term OS analysis was conducted in all randomized patients. 127 patients did not have additional survival data and remained censored, with survival time unchanged from the planned final OS analysis until May 4, 2026.

Final safety data for ADAURA were collected at the planned final OS analysis, at which time the safety and tolerability of TAGRISSO were consistent with its established profile with no new safety concerns.

Complementing the ADAURA clinical trial findings, real-world evidence presented at WCLC26 from a retrospective cohort study of US patients with early-stage (I-IIIA) EGFRm NSCLC (Abstract P1.142) showed that early discontinuation of TAGRISSO before completion of the three-year treatment course more than doubled the risk of disease recurrence or death. These results reinforce the importance of maintaining the full treatment duration established in ADAURA and underscore the need for clinician-patient communication to support treatment persistence.

In the advanced disease setting, additional data presented at WCLC26 from the FLAURA2 Phase III trial reinforced the benefits of backbone therapy TAGRISSO in combination with platinum-pemetrexed chemotherapy in patients with 1st-line advanced EGFRm NSCLC. Results from a novel safety analysis (Abstract PT2.03.03) showed that with long-term follow-up (median 42.6 months), the safety and tolerability of TAGRISSO plus platinum–pemetrexed remained consistent with the established safety profiles of these medicines, with clear reductions in new adverse event onset following the initial induction period. Additionally, an exploratory analysis (Abstract P2.237) showed that progression-free survival and OS HRs numerically favored TAGRISSO plus platinum–pemetrexed versus TAGRISSO monotherapy regardless of baseline TP53 co-mutation status.

IMPORTANT SAFETY INFORMATION

  • There are no contraindications for TAGRISSO

  • TAGRISSO can cause severe and fatal interstitial lung disease (ILD)/pneumonitis. ILD/pneumonitis occurred in 4% of the 1813 patients treated with TAGRISSO monotherapy who had not received recent definitive chemoradiation therapy; 0.4% of cases were fatal

ILD/Pneumonitis with TAGRISSO in combination with Pemetrexed and Platinum-based Chemotherapy:

  • In the FLAURA2 study, ILD/pneumonitis occurred in 3.3% of the 276 patients who received TAGRISSO in combination with pemetrexed and platinum-based chemotherapy; 0.4% of cases were fatal

ILD/Pneumonitis Following Definitive Platinum-based Chemoradiation Therapy (CRT):

  • In the LAURA study, following definitive platinum-based CRT, ILD/pneumonitis including radiation pneumonitis, occurred in 80 of the 143 patients (56%) who received TAGRISSO monotherapy and 28 of the 73 patients (38%) who received placebo. There was one fatal case (0.7%), 3.5% Grade 3, 34% Grade 2, and 18% Grade 1 adverse reactions of ILD/pneumonitis in TAGRISSO-treated patients. For TAGRISSO-treated patients, ILD/pneumonitis led to permanent discontinuation of TAGRISSO in 7% of patients and dosage interruptions of TAGRISSO in 35% of patients. Among the 46 patients who were rechallenged with TAGRISSO, 11% had recurrence of ILD/pneumonitis. In the 80 TAGRISSO-treated patients, ILD/pneumonitis resolved in 40%, resolved with sequelae in 1.3%, were resolving in 16%, did not resolve in 41%, and resulted in death in 1.3%

For patients receiving TAGRISSO who have not received recent definitive platinum-based CRT, withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Permanently discontinue TAGRISSO if ILD/pneumonitis is confirmed. For patients who have received recent definitive platinum-based CRT with Grade 1 ILD/pneumonitis, continue TAGRISSO or interrupt and restart, as appropriate. Permanently discontinue TAGRISSO in patients diagnosed with Grade ≥2 ILD/pneumonitis

  • TAGRISSO can cause heart rate-corrected QT (QTc) interval prolongation. Of the 1813 TAGRISSO monotherapy-treated patients in clinical trials, 1.1% were found to have a QTc >500 msec, and 4.3% of patients had an increase from baseline QTc >60 msec. Of the 276 patients treated with TAGRISSO in combination with pemetrexed and platinum-based chemotherapy in the FLAURA2 study, 1.8% were found to have a QTc >500 msec, and 10.5% of patients had an increase from baseline QTc >60 msec. No QTc-related arrhythmias were reported. Clinical trials of TAGRISSO did not enroll patients with baseline QTc of >470 msec. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia

  • TAGRISSO can cause cardiomyopathy, including cardiac failure, chronic cardiac failure, congestive heart failure, pulmonary edema or decreased ejection fraction. Cardiomyopathy occurred in 3.8% of the 1813 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. In the FLAURA2 study, cardiomyopathy occurred in 9% of the 276 patients who received TAGRISSO in combination with pemetrexed and platinum-based chemotherapy; 1.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred in 4.2% of 1557 patients who had baseline and at least one follow-up LVEF assessment. In the ADAURA study, 1.5% (5/325) of TAGRISSO-treated patients experienced LVEF decreases ≥10% from baseline and a drop to <50%. In the LAURA study, following platinum-based CRT, 3% (4/135) of TAGRISSO-treated patients and no placebo-treated patients experienced LVEF decreases ≥10% and a drop to <50%. In the FLAURA2 study, 8% (21/262) of patients treated with TAGRISSO in combination with pemetrexed and platinum- based chemotherapy, who had baseline and at least one follow-up LVEF assessment, experienced LVEF decreases ≥10% and a drop to <50%. For patients receiving TAGRISSO monotherapy, conduct cardiac monitoring in patients with cardiac risk factors, including assessment of LVEF at baseline and during treatment. For patients receiving TAGRISSO in combination with pemetrexed and platinum-based chemotherapy, conduct cardiac monitoring in all patients, including assessment of LVEF at baseline and during treatment. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure, permanently discontinue TAGRISSO

  • Keratitis was reported in 0.6% of 1813 patients treated with TAGRISSO monotherapy in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) to an ophthalmologist

  • Postmarketing cases consistent with erythema multiforme major (EMM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if EMM, SJS, or TEN is suspected and permanently discontinue if confirmed

  • Postmarketing cases of cutaneous vasculitis including leukocytoclastic vasculitis, urticarial vasculitis, and IgA vasculitis have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if cutaneous vasculitis is suspected, evaluate for systemic involvement, and consider dermatology consultation. If no other etiology can be identified, consider permanent discontinuation of TAGRISSO based on severity

  • Aplastic anemia has been reported in TAGRISSO-treated patients in clinical trials (0.06% of 1813) and postmarketing. Some cases had a fatal outcome. Inform patients of the signs and symptoms of aplastic anemia including but not limited to, new or persistent fevers, bruising, bleeding, and pallor. If aplastic anemia is suspected, withhold TAGRISSO and obtain a hematology consultation. If aplastic anemia is confirmed, permanently discontinue TAGRISSO. Perform complete blood count with differential before starting TAGRISSO, periodically throughout treatment, and more frequently if indicated

  • Verify pregnancy status of females of reproductive potential prior to initiating TAGRISSO. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAGRISSO and for 6 weeks after the last dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the last dose

  • Because of the potential for serious adverse reactions in breastfed infants from TAGRISSO, women should not breastfeed during treatment with TAGRISSO and for 2 weeks after the last dose

  • Most common (≥20%) adverse reactions, including laboratory abnormalities, were:

    • TAGRISSO monotherapy: leukopenia, lymphopenia, thrombocytopenia, anemia, diarrhea, rash, musculoskeletal pain, neutropenia, nail toxicity, dry skin, stomatitis, and fatigue

    • TAGRISSO monotherapy following platinum-based chemoradiation therapy: lymphopenia, leukopenia, ILD/pneumonitis, thrombocytopenia, neutropenia, rash, diarrhea, nail toxicity, musculoskeletal pain, cough and COVID-19

    • TAGRISSO in combination with pemetrexed and platinum-based chemotherapy: leukopenia, thrombocytopenia, neutropenia, lymphopenia, rash, diarrhea, stomatitis, nail toxicity, dry skin, and increased blood creatinine

INDICATIONS

  • TAGRISSO is indicated as adjuvant therapy after tumor resection in adult patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test

  • TAGRISSO is indicated for the treatment of adult patients with locally advanced, unresectable (stage III) NSCLC whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy and whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test

  • TAGRISSO is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test

  • TAGRISSO is indicated in combination with pemetrexed and platinum-based chemotherapy, for the first-line treatment of adult patients with locally advanced or metastatic NSCLC whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test

  • TAGRISSO is indicated for the treatment of adult patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy

Please see complete Prescribing Information, including Patient Information for TAGRISSO.

Notes

NSCLC

Lung cancer is the leading cause of cancer death globally, accounting for almost one in five (19%) cancer deaths.1-2 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% of patients diagnosed with NSCLC.3 Approximately 75% of NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.4-5 Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.6

For patients with resectable tumors, the majority eventually develop recurrence despite complete tumor resection and adjuvant chemotherapy.7 Further, 73% of patients with Stage IB and 56-65% of patients with Stage II disease will survive for five years. This decreases to 41% for patients with Stage IIIA.8

Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.9-11 These patients are particularly sensitive to treatment with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) which block the cell-signaling pathways that drive the growth of tumor cells.12

ADAURA

ADAURA was a randomized, double-blind, placebo-controlled, global Phase III trial in the adjuvant treatment of 682 patients with Stage IB, II, IIIA EGFRm NSCLC following complete tumor resection and, at physicians’ and patients’ discretion, adjuvant chemotherapy. Patients were treated with TAGRISSO80 mg once-daily oral tablets or placebo for three years or until disease recurrence.

The trial was enrolled in more than 200 centers across more than 20 countries, including the US, Europe, South America, Asia and the Middle East. The primary endpoint was disease-free survival (DFS) in Stage II and IIIA patients and key secondary endpoints included DFS in Stage IB, II and IIIA patients, and OS in both the primary and overall populations.

The exploratory analysis presented at WCLC26 was conducted in all randomized patients including complete or partial extended long-term survival data from approximately 77% of those patients who were still alive at the final planned OS analysis DCO. This included trial participants with additional survival data up until the May 4, 2026 DCO or from accessible medical records/information from last contact date. 127 patients did not have additional survival data and remained censored, with survival time unchanged from the planned final OS analysis until May 4, 2026.

TAGRISSO® (osimertinib)

TAGRISSO® (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including the treatment of central nervous system metastases. TAGRISSO (40 mg and 80 mg QD oral tablets) has been used to treat more than one million patients across its indications worldwide and AstraZeneca continues to explore TAGRISSO as a treatment for patients across multiple stages of EGFRm NSCLC.

TAGRISSO is approved as monotherapy in more than 120 countries including the US, EU, China and Japan. Approved indications include for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC, locally advanced or metastatic EGFR T790M mutation-positive NSCLC, adjuvant treatment of early-stage EGFRm NSCLC and locally advanced, unresectable NSCLC following platinum-based chemoradiation therapy. TAGRISSO is also approved in combination with chemotherapy in more than 80 countries, including the US, EU, China and Japan, for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC.

There is an extensive body of evidence supporting the use of TAGRISSO in EGFRm NSCLC, and it is the only targeted therapy shown to improve patient outcomes across all stages of the disease.

In late-stage disease, TAGRISSO demonstrated improved outcomes as monotherapy in the FLAURA Phase III trial and in combination with chemotherapy in the FLAURA2 Phase III trial. TAGRISSO is also being investigated in this setting in combination with savolitinibin the SAFFRON Phase III trial and in combination with datopotamab deruxtecan-dlnk in the TROPION-Lung14 and TROPION-Lung15 Phase III trials.

In addition to ADAURA, TAGRISSO also showed improved outcomes in early-stage disease in the NeoADAURA Phase III trial and in locally advanced stages in the LAURA Phase III trial. As part of AstraZeneca’s ongoing commitment to treating patients as early as possible in lung cancer, TAGRISSO is also being investigated in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial.

AstraZeneca in lung cancer

AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most.

The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including TAGRISSO and gefitinib; sunvozertinib;durvalumab and tremelimumab-actl; fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan-dlnkin collaboration with Daiichi Sankyo; savolitinib in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.

AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment.

AstraZeneca in oncology

AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

AstraZeneca

AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca-us.com and follow the Company on social media @AstraZeneca.

References

  1. World Health Organization. International Agency for Research on Cancer. All Cancers Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/39-all-cancers-fact-sheet.pdf. Accessed September 2026.

  2. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf. Accessed September 2026.

  3. American Cancer Society. What Is Lung Cancer? Available at: https://www.cancer.org/cancer/types/lung-cancer/about/what-is.html. Accessed September 2026.

  4. Chen HJ, et al. Long-term survival of advanced lung adenocarcinoma by maintenance chemotherapy followed by EGFR-TKI. Medicine. 2021;100(6):e24688.

  5. Barcellini L, et al. Immune Checkpoint Inhibitors and Targeted Therapies in Early-Stage Non-Small-Cell Lung Cancer: State-of-the-Art and Future Perspectives. Cancers (Basel). 2025;17(4):652.

  6. Sethi S, et al. Incidental Nodule Management – Should There Be a Formal Process? J Thorac Dis. 2016:8(Suppl 6);S494-S497.

  7. Provencio M, et al. Treatment Sequencing in Resectable Lung Cancer: The Good and the Bad of Adjuvant Versus Neoadjuvant Therapy. Am Soc Clin Oncol Educ Book. 2022;42:1-18.

  8. Goldstraw P, et al. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. J Thorac Oncol. 2016;11(1):39-51.

  9. Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on Cytological and Histological Samples in Non-Small Cell Lung Cancer: a Polish, Single Institution Study and Systematic Review of European Incidence. Int J Clin Exp Pathol. 2013;6:2800-2812.

  10. Keedy VL, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell Lung Cancer Considering First- Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011;29:2121-2127.

  11. Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a Review of Available Methods and Their Use for Analysis of Tumour Tissue and Cytology Samples. J Clin Pathol. 2013;66:79-89.

  12. Cross DA, et al. AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer. Cancer Discov. 2014;4(9):1046-1061.

US-115883 Last Updated 9/26

Media Inquiries

Lauren-Jei McCarthy

+1 347 918 7001

US Media Mailbox: [email protected]

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INDUSTRY KEYWORDS: Oncology Health Clinical Trials Research Science Pharmaceutical Biotechnology

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Zipalertinib Plus Chemotherapy Demonstrates 6-Month Median Progression-Free Survival Benefit in REZILIENT3 Phase 3 Trial in First-Line EGFR Exon 20 Insertion Mutation Non-Small Cell Lung Cancer

Zipalertinib Plus Chemotherapy Demonstrates 6-Month Median Progression-Free Survival Benefit in REZILIENT3 Phase 3 Trial in First-Line EGFR Exon 20 Insertion Mutation Non-Small Cell Lung Cancer

Results from the Phase 3 REZILIENT3 trial were featured in a Presidential Symposium at WCLC 2026 and demonstrated a statistically significant improvement in progression-free survival in first-line EGFR exon 20 insertion mutation NSCLC at a planned interim analysis

PRINCETON, N.J. & TOKYO & CAMBRIDGE, Mass.–(BUSINESS WIRE)–
Taiho Oncology, Inc., Taiho Pharmaceutical Co., Ltd., and Cullinan Therapeutics, Inc. (Nasdaq: CGEM) today announced results from the Phase 3 REZILIENT3 trial evaluating zipalertinib plus chemotherapy versus chemotherapy alone in the first-line treatment of patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutation-positive non-small cell lung cancer (NSCLC). The data were presented at the International Association for the Study of Lung Cancer’s (IASLC) 2026 World Conference on Lung Cancer (WCLC) in Seoul, South Korea.

As previously announced, REZILIENT3 met its primary endpoint of progression-free survival (PFS). The results released today show that the addition of zipalertinib to platinum-based chemotherapy provided a statistically significant and clinically meaningful median PFS improvement of 6.0 months (HR=0.50; 95% CI, 0.34-0.73; P=0.00015) as first-line treatment for advanced NSCLC patients with EGFR ex20ins mutations. At the interim overall survival analysis (30% event maturity), the hazard ratio for death for zipalertinib plus chemotherapy versus chemotherapy was 0.72 (95% CI, 0.42-1.23) with follow up ongoing.

“The combination of zipalertinib plus platinum-based chemotherapy in the REZILIENT3 trial demonstrated a statistically significant and clinically meaningful improvement in progression-free survival for patients with advanced non-small cell lung cancer harboring EGFR exon 20 insertion mutations,” said Helena A. Yu, MD, Thoracic Medical Oncologist at Memorial Sloan Kettering Cancer Center and study investigator. “The combination also produced significantly higher response rates compared with chemotherapy alone. These findings support the potential of zipalertinib plus platinum-based chemotherapy as a first-line treatment option for this patient population. We are grateful to the patients and their families, as well as the investigators whose dedication made these results possible.”

These late-breaking results from the planned interim analysis of REZILIENT3 were selected for presentation in the Presidential Symposium 2 at IASLC 2026 WCLC. The Presidential Symposium 2 is a premier plenary session featuring notable advances in lung cancer research and treatment with the potential to change clinical practice.

“The findings presented add to previously presented single agent zipalertinib data and support the potential of zipalertinib across multiple treatment settings. We are thankful to patients, their families, and caregivers for participation in REZILIENT3,” said Harold Keer, MD, PhD, Chief Medical Officer of Taiho Oncology. “We are excited to discuss these results further with health authorities and collaborate to make zipalertinib available to patients in a timely manner.”

“We believe these results mark a potentially important step forward in the treatment of EGFR exon 20 insertion mutation-positive non-small cell lung cancer,” said Fabio Benedetti, MD, Global Chief Medical Officer, Taiho Pharmaceutical. “To address the unmet medical needs of patients and their families, we will continue working closely with Taiho Oncology and Cullinan to make this treatment available to patients who may benefit from it.”

“The selection of REZILIENT3 for presentation in a Presidential Symposium reflects the importance of these findings for the lung cancer community,” said Jeffrey Jones, MD, MBA, Chief Medical Officer, Cullinan Therapeutics. “The magnitude of progression-free survival benefit, together with improvements in response rates and duration of response seen in REZILIENT3, reinforce the potential for zipalertinib plus chemotherapy to play an important role in the first-line treatment of patients with EGFR exon 20 insertion mutation NSCLC.”

Summary of Results:

After a safety lead-in (n=6), a total of 279 advanced NSCLC patients with EGFR ex20ins and no prior treatment for advanced disease were randomly assigned to receive zipalertinib 100mg BID plus chemotherapy (n=140) or chemotherapy alone (n=139). Baseline characteristics were balanced between the combination and the control arm, including age (66.5 vs. 64 years), sex (65.7% vs. 63.3% female), and brain metastases (31.4% vs. 31.7%), respectively.

At the pre-planned interim efficacy analysis after 122 PFS events, treatment with zipalertinib plus chemotherapy led to significantly longer median PFS than chemotherapy alone (14.5 vs. 8.5 months; HR: 0.50; 95% CI 0.34-0.73; P=0.00015). This PFS benefit was consistent across subgroups, including patients with brain metastases (HR: 0.38).

Objective response rate was higher with the combination therapy (65.0% vs. 40.3%), P<0.0001, with a longer median duration of response (14.2 vs. 9.9 months). At the interim overall survival (OS) analysis (30% maturity), the hazard ratio for death for zipalertinib plus chemotherapy as compared with chemotherapy was 0.72 (95% CI, 0.42-1.23). Continued follow-up of REZILIENT3 is ongoing to further characterize the OS benefit and exploratory endpoints (ClinicalTrials.gov number NCT05973773).

Summary of Preliminary Safety and Tolerability:

The observed adverse event (AE) profile of zipalertinib plus chemotherapy was generally consistent with the known safety profiles of the individual agents, and no new safety signals were observed. Grade ≥3 AEs occurred more frequently with the combination (87.1% vs. 54.4%), but these were primarily manageable hematologic AEs (58.6% vs. 28.7%). Grade ≥3 EGFR-related toxicities were infrequent, and those observed only in the combination arm included rash (10.7%) and diarrhea (1.4%).

Session information for the data presentation at WCLC 2026 is listed below:

Title:Zipalertinib plus Chemotherapy for 1st-line NSCLC with EGFR Exon 20 Insertions: Results from the Phase 3 Trial (REZILIENT3)

Presenting Author: Dr. Daniel Tan Shao Weng, Duke Health, Singapore

Session Name: PL03 Presidential Symposium 2 Including Lectureship Award Presentations

Session Type: Presidential Symposium 2, a premier plenary session featuring notable advances in lung cancer research and treatment

Session Date: Monday, September 14, 2026

Session Time: 8 a.m. KST

Location: Plenary, Hall D2, 3F

About the REZILIENT3 Trial

This multicenter, randomized, controlled, open-label global trial enrolled 285 adults with previously untreated, locally advanced or metastatic non-squamous NSCLC with EGFR exon 20 insertion mutations. The primary objective of this trial is to assess progression-free survival in the zipalertinib plus chemotherapy arm versus the chemotherapy arm.

About Zipalertinib

Zipalertinib (development code: CLN-081/TAS6417) is an orally available small molecule designed to target activating mutations in EGFR. The molecule was selected because of its ability to inhibit EGFR variants with exon 20 insertion mutations. Zipalertinib is designed as a next generation, irreversible EGFR inhibitor for the treatment of a genetically defined subset of patients with non-small cell lung cancer. Zipalertinib is investigational and has not been approved by any health authority.

Zipalertinib is being developed by Taiho Oncology, Inc., its parent company, Taiho Pharmaceutical Co., Ltd., and in collaboration with Cullinan Therapeutics, Inc. in the U.S.

About EGFR Exon 20 Insertion Mutations

NSCLC is a common form of lung cancer and up to 4% of all cases globally have EGFR ex20ins.1 In the United States, approximately 16% of patients with NSCLC harbor EGFR mutations,1 with insertions at exon 20 accounting for up to 12% of these mutations.2

About Taiho Oncology, Inc.

The mission of Taiho Oncology, Inc. is to improve the lives of patients with cancer, their families and their caregivers. The company specializes in the development and commercialization of orally administered anti-cancer agents for various tumor types. Taiho Oncology has a robust pipeline of small-molecule clinical candidates targeting solid-tumor and hematological malignancies, with additional candidates in pre-clinical development. Taiho Oncology is a subsidiary of Taiho Pharmaceutical Co., Ltd. which is part of Otsuka Holdings Co., Ltd. Taiho Oncology is headquartered in Princeton, New Jersey and oversees its parent company’s European and Canadian operations, which are located in Baar, Switzerland and Oakville, Ontario, Canada.

For more information, visit https://www.taihooncology.com/us, and follow us on LinkedIn and X.

Taiho Oncology and the Taiho Oncology logo are registered trademarks of Taiho Pharmaceutical Co., Ltd.

About Taiho Pharmaceutical Co., Ltd. (Japan)

Taiho Pharmaceutical, a subsidiary of Otsuka Holdings Co., Ltd. (https://www.otsuka.com/en/), is an R&D-driven specialty pharma focusing on the fields of oncology and immune-related diseases. Its corporate philosophy takes the form of a pledge: “We strive to improve human health and contribute to a society enriched by smiles.” In the field of oncology, in particular, Taiho Pharmaceutical is known as a leading company in Japan for developing innovative medicines for the treatment of cancer, a reputation that is rapidly expanding through their extensive global R&D efforts. In areas other than oncology, as well, the company creates and markets quality products that effectively treat medical conditions and can help improve people’s quality of life. Always putting customers first, Taiho Pharmaceutical also aims to offer consumer healthcare products that support people’s efforts to lead fulfilling and rewarding lives. For more information about Taiho Pharmaceutical, please visit https://www.taiho.co.jp/en.

About Cullinan Therapeutics

Cullinan Therapeutics, Inc. (Nasdaq: CGEM) is a biopharmaceutical company developing potential first- or best-in-class, disease-modifying T cell engagers for autoimmune diseases and cancer. Cullinan pursues promising therapeutic targets while leveraging core expertise in T cell engagers, which are established in oncology and are now advancing into autoimmune diseases. With a clinical-stage pipeline built on a rigorous scientific approach and purposeful innovation, Cullinan is advancing its mission to deliver new standards of care for patients. Learn more about Cullinan at https://cullinantherapeutics.com/, and follow Cullinan on LinkedIn and X.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements regarding the company’s beliefs and expectations regarding the clinical development of zipalertinib, the safety and efficacy profile of zipalertinib and its potential to address unmet medical need, the potential of zipalertinib to become a first-line treatment option and other statements that are not historical facts. The words “believe,” “continue,” “could,” “estimate,” “expect,” “intends,” “may,” “plan,” “potential,” “project,” “pursue,” “will,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.

Any forward-looking statements in this press release are based on management’s current expectations and beliefs of future events and are subject to known and unknown risks and uncertainties that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These risks include, but are not limited to, the following: uncertainty regarding the timing and results of clinical trial data and regulatory submissions; the risk that any NDAs, INDs or other global regulatory submissions we may file with the United States Food and Drug Administration or other global regulatory agencies are not accepted or cleared on our expected timelines, or at all; the success of our clinical trials and preclinical studies; the risks related to our ability to protect and maintain our intellectual property position; the risks related to manufacturing, supply, and distribution of our product candidates; the risk that any one or more of our product candidates, including those that are co-developed, will not be successfully developed and commercialized; the risk that the results of preclinical studies or clinical trials will not be predictive of future results in connection with future studies or clinical trials; the effect of changes in global economic conditions, including uncertainties related to international trade policies, tariffs and supply chain dynamics on our business and operations; and the success of any collaboration, partnership, license or similar agreements. These and other important risks and uncertainties discussed in our filings with the Securities and Exchange Commission, including under the caption “Risk Factors” in our most recent Annual Report on Form 10-K and subsequent filings with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change, except to the extent required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Moreover, except as required by law, neither the company nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made.

References

  1. Burnett H, Emich H, Carroll C, et al. Epidemiological and clinical burden of EGFR exon 20 insertion in advanced non-small cell lung cancer: a systematic literature review. PLOS ONE. 2021;16(3): e0247620. Available at: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247620.

  2. Riess JW, Gandara DR, Frampton GM, et al. Diverse EGFR Exon 20 Insertions and Co-Occurring Molecular Alterations Identified by Comprehensive Genomic Profiling of NSCLC. Journal of Thoracic Oncology. 2018 Jul 5;13(10):1560–1568. Available at: https://www.jto.org/article/S1556-0864(18)30770-6/pdf.

Taiho Oncology

Leigh Labrie

+1 609.664.9878

[email protected]

Taiho Pharmaceutical Co., Ltd.

Junko Onishi

+81-80-1009-7683

[email protected]

Cullinan Therapeutics

Investors

Nick Smith

+1 401.241.3516

[email protected]

Media

Rose Weldon

+1 215.801.7644

[email protected]

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INDUSTRY KEYWORDS: Research Clinical Trials Other Health Biotechnology General Health Pharmaceutical Health Science Oncology Other Science

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Baker Hughes and Venture Global Advance Next Phase of U.S. Gas Infrastructure Growth

  • Secured a substantial order to supply gas compression systems for the Cloud Connector Pipeline project
  • Awarded a major order for a modular liquefaction solution supporting Plaquemines LNG facility expansion
  • Awards deepen long-standing strategic collaboration with Venture Global

HOUSTON and LONDON, Sept. 13, 2026 (GLOBE NEWSWIRE) — Baker Hughes (NASDAQ: BKR) and Venture Global LNG are expanding their long-standing collaboration to advance critical U.S. gas infrastructure. Reinforcing Baker Hughes’ connected capabilities across the natural gas value chain, the company will provide gas compression systems for the Cloud Connector Pipeline project in Louisiana, as well as a modular liquefaction solution including cold boxes to support the expansion of the Plaquemines LNG facility.

Together, the pipeline and liquefaction awards demonstrate the critical role of integrated natural gas infrastructure in expanding LNG supply and enhancing energy security for global markets. The substantial pipeline award, which includes 13 gas compression systems driven by Frame 5/2E gas turbines, represents one of the largest deployments for LNG feed gas transportation in the United States. This will enable reliable and efficient transportation of feed gas through the Cloud Connector Pipeline to Venture Global’s Plaquemines facility.

Under the major liquefaction award, Baker Hughes will provide four liquefaction blocks, comprising a total of eight liquefaction modules, to support additional LNG production capacity at Plaquemines LNG facility. The liquefaction blocks include Chart cold boxes.

“Baker Hughes has been a trusted partner across our LNG developments, both at our LNG facilities and across our pipeline infrastructure,” said Mike Sabel, CEO of Venture Global. “As we advance the expansion of Plaquemines LNG, this collaboration not only supports our expansion plans, but also helps ensure we deliver the reliable feed gas transportation necessary to realize our mission of supplying secure LNG to global markets.”

“U.S. natural gas is helping to deliver the energy continuity required for industries, communities, and economies to thrive, grow and innovate. Baker Hughes is proud to work alongside our partners at Venture Global as they expand Plaquemines LNG, providing the critical energy infrastructure needed to meet growing global long-term global energy demand,” said Lorenzo Simonelli, chairman and CEO of Baker Hughes.

The liquefaction solution provided by Baker Hughes for the Plaquemines expansion follows a similar scope recently awarded for the CP2 project. Each liquefaction block is based on two electric-motor driven, single mixed-refrigerant (SMR) liquefaction modules and associated compression trains featuring Baker Hughes’ advanced centrifugal compressor technology, as well as cold boxes, air coolers and integrated control systems.

The Cloud Connector award is the second order of Frame 5/2E gas turbine-driven centrifugal compressor packages for Venture Global’s feed gas pipeline, expanding the fleet to 23 Frame 5/2E-driven gas compression systems for the Plaquemines LNG facility. The award further strengthens Baker Hughes’ strategic relationship with Venture Global, supporting more than 100 MTPA of existing and planned LNG production capacity, and reinforces Baker Hughes’ role as a leading industrialized energy provider across the natural gas value chain.

About Baker Hughes

Baker Hughes (NASDAQ: BKR) is an energy technology company that provides solutions to energy and industrial customers worldwide. Built on a century of experience and conducting business in over 120 countries, our innovative technologies and services are taking energy forward – making it safer, cleaner and more efficient for people and the planet. Visit us at bakerhughes.com.

For more information, please contact:

Media Relations

Adrienne M. Lynch
+1 713-906-8407
[email protected]

Investor Relations

Chase Mulvehill
+1 346-297-2561
[email protected]



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Faraday Future Founder and Global CEO YT Jia Shares Weekly Investor Update: Previews the Upcoming 9/19 Event; Highlights FF’s EAI Robotics’ Autonomous Perception and 3D Scanning Technology; Adds a New Senior Advisor Focused on Govt. Procurement

Faraday Future Founder and Global CEO YT Jia Shares Weekly Investor Update: Previews the Upcoming 9/19 Event; Highlights FF’s EAI Robotics’ Autonomous Perception and 3D Scanning Technology; Adds a New Senior Advisor Focused on Govt. Procurement

  • On September 19 at 5:00 p.m. PT, FF will hold the FF EAI Robotics “Four-Core Full-Stack AI” Ecosystem New Product Series Launch where the Company will focus on launching products of two of its four cores: the EAI Devices core and the Industry Productivity Solutions core.
  • On September 28, FF will hold Part Two of its EAI Robotics “Built in USA” Launch and Business Partner Conference, focused on recruiting upstream partners to drive cooperation in U.S. local manufacturing, supply chain, product certification, and market access.
  • FF welcomes Steven Newton, Senior Advisor to the US General Services Administration and member of the Los Angeles Unified School District Procurement Committee as a senior advisor. Steven will be fully involved in FF’s business growth across government, public institutions, and education sectors.

LOS ANGELES–(BUSINESS WIRE)–Faraday Future Intelligent Electric Inc. (NASDAQ: FFAI) (“Faraday Future”, “FF” or the “Company”), a California-based global Embodied AI (EAI) ecosystem company, today shared a weekly business update from YT Jia, Founder and Global CEO of FF.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20260913091795/en/

Faraday Future Founder and Global CEO YT Jia Shares Weekly Investor Update: Previews the Upcoming 9/19 Event; Highlights FF’s EAI Robotics' Autonomous Perception and 3D Scanning Technology; Adds a New Senior Advisor Focused on Govt. Procurement

Faraday Future Founder and Global CEO YT Jia Shares Weekly Investor Update: Previews the Upcoming 9/19 Event; Highlights FF’s EAI Robotics’ Autonomous Perception and 3D Scanning Technology; Adds a New Senior Advisor Focused on Govt. Procurement

“Hello, everyone. Welcome to Issue 72 of our Weekly Report. Our annual 9/19 event is almost here. On September 19 at 5:00 p.m. Pacific Time, we will hold the FF EAI Robotics “Four-Core Full-Stack AI” Ecosystem New Product Series Launch. We will focus on launching products of two of our four cores: the EAI Devices core and the Industry Productivity Solutions core.

For the EAI Devices, we will unveil and bring to market nine new robot devices. This will include the final launch of the All-New Futurist, which will officially go on sale. With this, the “One-Brain Multi-Form Multi-Capability” FF EAI Robot World 2.0 will be complete. We will also become the U.S. robotics company with the widest range of device forms, sizes, and models. Our devices will cover three forms: humanoids, quadrupeds, and mobile manipulators. They will come in large, medium, and small sizes. This gives our FF Robot World more complete device support for deployment across different industry ecosystems and use cases.

For the Industry Productivity Solutions, we will launch four complete solutions: K-12 education, research, security, and inspection. This moves FF from device deployment to complete solution delivery. This will make it easier for customers to deploy and use robots, while giving the industry a practical model that can be replicated at scale.

Next, I want to highlight one of the fundamental technologies behind our security and inspection solutions: FF EAI Robotics’ autonomous perception and 3D scanning technology. This is a self-developed “One Brain, Multiple Forms” technology which uses multi-sensor fusion and SLAM, Simultaneous Localization and Mapping. This lets the robot sense its environment, know its location, and follow the right path. Our team can set the route, checkpoints, and no-go zones in advance; then the robot can carry out tasks on its own. If it meets people, vehicles, or temporary obstacles along the way, it can slow down, stop, go around them, avoid them, or re-plan its route. In security use cases, it can patrol on its own, spot anomalies, and raise an alert. In inspection use cases, it can reach set checkpoints, collect equipment data, monitor for changes, and flag potential risks.

These autonomous, practical capabilities in real-world settings will greatly cut down on repetitive work and constant remote control for our users, raising efficiency and lowering operational risk. At the same time, this technology works across different robot forms, further supporting our “One Brain, Multiple Forms; Multiple Forms, Multiple Capabilities” roadmap, as real task data keeps feeding back into our models, devices, and solutions, speeding up the evolutionary flywheel of our “Four-Core Full-Stack AI” ecosystem. We will officially reveal more details on our technology and new products at the 9/19 launch event, and we hope you’ll tune in.

On September 28, we will also hold Part Two of our EAI Robotics “Built in USA” Launch and Business Partner Conference, focused on recruiting upstream partners and sharing more details on the execution of our acceleration program, to drive cooperation in U.S. local manufacturing, supply chain, product certification, and market access. Around the same time, FF will exhibit at IROS 2026 in Pittsburgh, one of the largest and most influential robotics conferences in the world. From September 28 to 30, come visit us at Booth 932 to see our robots up close and talk with them.

Regarding the S7 system build-up, Steven Newton, Senior Advisor to the US General Services Administration and member of the Los Angeles Unified School District Procurement Committee, has officially become a Senior Strategic Advisor to FF. Steven brings more than 25 years of experience in government procurement access and has worked in U.S. education for decades. Working with him is an important step for FF as we enter the U.S. federal government procurement directory and keep growing our education business nationwide. Steven will be fully involved in FF’s business growth across government, public institutions, and education sectors, focusing on government procurement access, our partnership with LAUSD, and market development in K-12 and higher education. He will also serve as an FF Executive Mentor, deeply empowering our user ecosystem build-up and expanding our business partnerships. Regarding AIxC, RoboShare continues to refine merchant onboarding, robot asset management, and leasing functions this week, accelerating the expansion of third-party operators, lessors, and distributors. Its goal is adding 3 new partners this month. Thank you, everyone. See you next week at our 9/19 event!”

ABOUT FARADAY FUTURE

Founded in 2014, Faraday Future (FF) is a U.S.-based Physical AI ecosystem company dedicated to reshaping the future of robotics and mobility solutions through AI innovation and technologies. FF focuses on two major product strategies within the Embodied AI (EAI) robotics business: EAI humanoid and bionic robots, and EAI automotive-focused robots. By building a “Four-Core Full-Stack AI” ecosystem of EAI Brain and Developer Platform, EAI Devices, Industry Productivity Solutions and EAI Data Factory, FF aims to create an evolutionary flywheel: scaled device delivery, data collection and training, continuous evolution of the EAI Brain, stronger product capability, and even larger-scale delivery and deployment. Through this flywheel, FF seeks to maximize its commercial value and lead to the advancement of Physical AI. For more information, please visit Faraday Future’s official website: https://www.ff.com/

FORWARD LOOKING STATEMENTS

Important factors, that may affect actual results or outcomes include, among others: the Company’s ability to continue as a going concern and improve its liquidity and financial position; the Company’s ability to pay its outstanding obligations, which it currently lacks; the availability of sufficient share capital to meet its current obligations and execute on its strategy; the willingness of convertible debt investors to fund the Company; demand for the Company’s robotics products; the ability of B2B preorder companies to locate customers to purchase our robotics products, on which their nonbinding preorders substantially depend; competition in the robotics industry, which includes companies with far superior experience, funding and name recognition; the ability of the Company to build an EAI education ecosystem that serves both the B2C consumer market and the B2B institutional education market; the acceptance by teachers and students of the Company’s robotics products in the education market; the ability of the Company to expand into additional markets for its robotics products; the Company’s reliance on a single OEM for most of its robotics products; the Company’s reliance on Chinese OEMs for all of its robotics products; the possibility of the federal government banning imports of Chinese robotics products; the Company’s ability to get the planned robotics products to comply with all applicable U.S. rules and regulations; the ability of the robotics OEM to timely supply robotics to the Company; tariff uncertainty for imported products, particularly from China; demand from automobile dealers for robotics products; the Company’s ability to homologate FX vehicles for sale; the Company’s ability to secure the necessary funding to execute on the FX strategy, which is substantial; the Company’s ability to secure an occupancy certificate covering all of its Hanford facility; the Company’s ability to remediate its material weaknesses in internal control over financial reporting and the risks related to the restatement of previously issued consolidated financial statements; the Company’s limited operating history and the significant barriers to growth it faces; the Company’s history of substantial losses and expectation of continued losses; the success of the Company’s payroll expense reduction plan; the Company’s ability to execute on its plans to develop and market its vehicles and the timing of these development programs; the Company’s estimates of the size of the markets for its vehicles and cost to bring those vehicles to market; the rate and degree of market acceptance of the Company’s vehicles; the Company’s ability to cover future warranty claims; the success of other competing manufacturers; the performance and security of the Company’s vehicles; current and potential litigation involving the Company; the Company’s ability to receive funds from, satisfy the conditions precedent of and close on the various financings described elsewhere by the Company; the result of future financing efforts, the failure of any of which could result in the Company seeking protection under the Bankruptcy Code; the Company’s indebtedness; the Company’s ability to use its “at-the-market” program; insurance coverage; general economic and market conditions impacting demand for the Company’s products; potential negative impacts of a reverse stock split; potential cost, headcount and salary reduction actions may not be sufficient or may not achieve their expected results; circumstances outside of the Company’s control, such as natural disasters, climate change, health epidemics and pandemics, terrorist attacks, and civil unrest; risks related to the Company’s operations in China; the success of the Company’s remedial measures taken in response to the Special Committee findings; the Company’s dependence on its suppliers and contract manufacturer; the Company’s ability to develop and protect its technologies; the Company’s ability to protect against cybersecurity risks; and the ability of the Company to attract and retain employees, any adverse developments in existing legal proceedings or the initiation of new legal proceedings, and volatility of the Company’s stock price. You should carefully consider the foregoing factors and the other risks and uncertainties described in the “Risk Factors” section of the Company’s Form 10-Q for the quarter ended June 30, 2026, filed with the SEC on August 13, 2026; the quarter ended March 31, 2026, filed with the SEC on May 14, 2026, and Form 10-K filed with the SEC on March 31, 2026, and other documents filed by the Company from time to time with the SEC.

Investors (English): [email protected]
Investors (Chinese): [email protected]
Media: [email protected]

KEYWORDS: United States North America Pennsylvania

INDUSTRY KEYWORDS: Primary/Secondary Robotics Education Technology Artificial Intelligence Drones Hardware

MEDIA:

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Faraday Future Founder and Global CEO YT Jia Shares Weekly Investor Update: Previews the Upcoming 9/19 Event; Highlights FF’s EAI Robotics’ Autonomous Perception and 3D Scanning Technology; Adds a New Senior Advisor Focused on Govt. Procurement
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Definium Therapeutics to Discuss Topline Results from Phase 3 Panorama Study in Generalized Anxiety Disorder on September 14, 2026

Definium Therapeutics to Discuss Topline Results from Phase 3 Panorama Study in Generalized Anxiety Disorder on September 14, 2026

Company to host webcast tomorrow at 8:00 a.m. EDT

NEW YORK–(BUSINESS WIRE)–
Definium Therapeutics, Inc. (“Definium” or the “Company”), a late-stage clinical biopharmaceutical company developing a new generation of therapeutics intended to address underlying causes of psychiatric and neurological disorders, today announced that it will host a live webcast tomorrow at 8 a.m. EDT to discuss topline results from Panorama, the Company’s second Phase 3 study of DT120 (lysergide) Orally Disintegrating Tablet (ODT) in adults with generalized anxiety disorder (GAD).

Webcast Details

Listeners can register for the webcast via this link. Analysts wishing to participate in the question-and-answer session should use this link. A replay of the webcast will be available via the Investor Relations section of the Definium Therapeutics website, ir.definiumtx.com, and archived for at least 30 days after the webcast. Those who plan on participating are advised to join 15 minutes prior to the start time.

About Panorama

Panorama (MM120-301) is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of DT120 Orally Disintegrating Tablet (ODT) in adults with generalized anxiety disorder (GAD). The study enrolled participants 18 to 74 years of age with a DSM-5-confirmed primary diagnosis of GAD and a minimum Hamilton Anxiety Rating Scale (HAM-A) total score of 20 at screening and baseline. Eligible participants were randomized 2:1:2 to receive a single dose of DT120 ODT 100 µg, DT120 ODT 50 µg, or matching placebo, with the 50 µg arm included to help mitigate functional unblinding. The study consists of a 12-week double-blind treatment period (Part A) followed by a 40-week open-label extension (Part B), during which participants may be eligible to receive up to four additional doses of DT120 ODT 100 µg based on symptom severity, for a total study duration of approximately 56 weeks. The primary endpoint is change from baseline in HAM-A total score at Week 12. Key secondary multiplicity-controlled endpoints are change from baseline in Clinical Global Impression-Severity (CGI-S) scale score at Week 12, change from baseline in HAM-A total score at Week 1, and change from baseline in CGI-S score at Day 2. Panorama enrolled 245 participants across approximately 32 study centers.

About Definium Therapeutics

The mission of Definium Therapeutics is to forge a new era of psychiatry by applying scientific rigor to psychedelics, with the goal of developing accessible treatments that unlock healing at scale. Guided by a recognition that patients deserve more than better, Definium is relentlessly advancing a new generation of therapeutics intended to address underlying causes of psychiatric and neurological disorders. By turning evidence into impact, Definium aims to change the trajectory of today’s mental health care crisis and enable a healthier future. Headquartered in New York, Definium Therapeutics trades on Nasdaq under the symbol DFTX.

Forward-Looking Statements

Certain statements in this news release related to the Company constitute “forward-looking information” within the meaning of applicable securities laws and are prospective in nature. Forward-looking information is not based on historical facts, but rather on current expectations and projections about future events and are therefore subject to risks and uncertainties which could cause actual results to differ materially from the future results expressed or implied by the forward-looking statements. These statements generally can be identified by the use of forward-looking words such as “will”, “may”, “should”, “could”, “intend”, “estimate”, “plan”, “anticipate”, “expect”, “believe”, “potential” or “continue”, or the negative thereof or similar variations. Forward-looking information in this news release includes, but is not limited to, the Company’s plans to host a live webinar to discuss topline results from the Phase 3 Panorama Study; and statements regarding the Company’s beliefs regarding potential benefits of DT120 ODT. There are numerous risks and uncertainties that could cause actual results and the Company’s plans and objectives to differ materially from those expressed in the forward-looking information, including history of negative cash flows; limited operating history; incurrence of future losses; availability of additional capital; compliance with laws and regulations; legislative and regulatory developments, including decisions by the Drug Enforcement Administration and states to reschedule any of our product candidates, if approved, containing Schedule I controlled substances, before they may be legally marketed in the U.S.; difficulty associated with research and development; risks associated with clinical studies or studies; heightened regulatory scrutiny; early stage product development; clinical study risks; regulatory approval processes; novelty of the psychedelic inspired medicines industry; ability to maintain effective patent rights and other intellectual property protection; as well as those risk factors discussed or referred to herein and the risks, uncertainties and other factors described in the Company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2025 and its Quarterly Reports on Form 10-Q for the fiscal quarters ended March 31, 2026 and June 30, 2026 under headings such as “Special Note Regarding Forward-Looking Statements,” and “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and other filings and furnishings made by the Company with the securities regulatory authorities in all provinces and territories of Canada which are available under the Company’s profile on SEDAR+ at www.sedarplus.ca and with the U.S. Securities and Exchange Commission on EDGAR at www.sec.gov. Except as required by law, the Company undertakes no duty or obligation to update any forward-looking statements contained in this release as a result of new information, future events, changes in expectations or otherwise.

Investors:

Gitanjali Jain

VP, Head of Investor Relations

[email protected]

Media:

[email protected]

KEYWORDS: New York United States North America

INDUSTRY KEYWORDS: Mental Health Research Neurology Clinical Trials Biotechnology Alternative Medicine Health Pharmaceutical Science

MEDIA:

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Ivonescimab Monotherapy Demonstrates a Statistically Significant & Clinically Meaningful Benefit Compared to Pembrolizumab Monotherapy in PD-L1-Positive Advanced NSCLC in Akeso’s HARMONi-2 Study Conducted in China

Ivonescimab Monotherapy Demonstrates a Statistically Significant & Clinically Meaningful Benefit Compared to Pembrolizumab Monotherapy in PD-L1-Positive Advanced NSCLC in Akeso’s HARMONi-2 Study Conducted in China

Ivonescimab Reduced the Risk of Death by 27% Compared to Pembrolizumab

HARMONi-2 Demonstrated an Improvement in Median Overall Survival of 8.2 Months

PD-L1 High Expression Subgroup: Hazard Ratio = 0.58

Summit is Conducting Global Phase III HARMONi-7 Study in Patients with PD-L1 High-Expressing NSCLC

MIAMI–(BUSINESS WIRE)–
Summit Therapeutics Inc. (NASDAQ: SMMT) today noted that its partner Akeso Inc. announced that updated data, including overall survival (OS), from the randomized, double-blind Phase III HARMONi-2 trial featuring the novel, potential first-in-class investigational bispecific antibody ivonescimab is being presented at the International Association for the Study of Lung Cancer’s (IASLC) 2026 World Conference on Lung Cancer (WCLC 2026) in Seoul, Republic of Korea.

The HARMONi-2 presentation entitled, Overall Survival Analysis From HARMONi-2: Ivonescimab vs Pembrolizumab as First-Line Treatment for PD-L1-Positive NSCLC, evaluated ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors have positive PD-L1 expression (PD-L1 Score >1%). HARMONi-2 (AK112-303) is a single-region, multi-center Phase III study conducted in China and sponsored by Akeso, with all relevant data exclusively generated, managed, and analyzed by Akeso.

The trial results will be presented by Professor Caicun Zhou, MD, PhD, Chief Physician and Director of the Department of Medical Oncology at Shanghai Pulmonary Hospital, Tongji University School of Medicine, and President of IASLC, on Tuesday September 15, 2026.

Clinically Meaningful Efficacy

In this protocol-specified interim analysis of OS, a secondary endpoint in the HARMONi-2 study, ivonescimab monotherapy demonstrated a statistically significant and clinically meaningful improvement compared to pembrolizumab monotherapy, achieving a hazard ratio (HR) of 0.73 (95% CI: 0.57, 0.95; p=0.009). A clinically meaningful benefit was demonstrated across important clinical subgroups, including those with PD-L1 low expression (PD-L1 Score 1-49%) and PD-L1 high expression (PD-L1 Score ≥ 50%), along with those with squamous and non-squamous histologies.

HARMONi-2 ITT (n=398)

Ivonescimab

Pembrolizumab

Median Follow-up: 36.0 mos

(n=198)

(n=200)

Median OS

30.8 mos

22.6 mos

OS Stratified HR

0.73

(95% CI: 0.57, 0.95; p=0.009)

ITT = intention-to-treat population; mos = months; CI = confidence interval

HARMONi-2 Subgroup Analyses; Ivonescimab vs. Pembrolizumab

Ivonescimab vs. Pembrolizumab

Descriptive, not formally powered

PD-L1 High (PD-L1 Score ≥50%)

HR = 0.58

n=168

(95% CI: 0.38, 0.89)

PD-L1 Low (PD-L1 Score 1-49%)

HR = 0.85

n=230

(95% CI: 0.61, 1.18)

Squamous Histology

HR = 0.65

n=181

(95% CI: 0.45, 0.95)

Non-Squamous Histology

HR = 0.79

n=217

(95% CI: 0.55, 1.14)

NR = not reached; mos = months; CI=confidence interval; n = number

Manageable Safety Profile

In this analysis, ivonescimab continued to demonstrate an acceptable and manageable safety profile in the HARMONi-2 study, which was consistent with previous Phase III studies of ivonescimab. No additional safety signals were noted in the HARMONi-2 study in this current data cut with longer treatment duration (median of 14 cycles of ivonescimab vs. 10 cycles of pembrolizumab) compared to the previous data cut.

Treatment-Related Adverse Events

Ivonescimab

(n=198)

Pembrolizumab

(n=200)

Median follow-up: 36.0 mos

Serious TRAEs, n (%)

59 (29.9)

43 (21.6)

TRAEs Leading to Discontinuation, n (%)

8 (4.1)

10 (5.0)

TRAEs = treatment-related adverse events; n = number; mos = months

Akeso received marketing authorization for ivonescimab from China’s National Medical Products Administration (NMPA) based on the results of HARMONi-2 in April 2025. In the study’s primary analysis, ivonescimab monotherapy demonstrated a statistically significant improvement in the trial’s primary endpoint, progression-free survival (PFS) by Independent Radiologic Review Committee (IRRC), when compared to pembrolizumab monotherapy, achieving a hazard ratio (HR) of 0.51 (95% CI: 0.38, 0.69; p<0.0001).1

“HARMONi-2 is the fourth Phase III study of ivonescimab to demonstrate statistically significant improvements for both overall survival and progression-free survival in head-to-head comparisons against standard-of-care regimens,” said Robert W. Duggan, Chairman and Co-Chief Executive Officer of Summit Therapeutics. “Demonstrating a survival benefit against pembrolizumab monotherapy in this setting further strengthens our conviction that ivonescimab has the potential to advance treatment beyond PD-1 blockade alone and define what a next-generation immuno-oncology therapy can deliver for patients with lung cancer.”

“Positive overall survival results in HARMONi-2 mark a pivotal moment for ivonescimab and underscore the promise of its differentiated PD-1 / VEGF bispecific approach,” said Dr. Maky Zanganeh, President and Co-Chief Executive Officer of Summit Therapeutics. “These data build on the study’s previously reported progression-free survival benefit, while further informing our confidence in the broader ivonescimab development program, including HARMONi-7, our ongoing global Phase III study evaluating ivonescimab monotherapy against pembrolizumab monotherapy in patients with PD-L1 high-expressing metastatic non-small cell lung cancer.”

Global Phase III HARMONi-7 Study

Based on the primary analysis results of HARMONi-2, Summit initiated the global HARMONi-7 study (NCT06767514) in early 2025. HARMONi-7 is a randomized, double-blind, multi-regional Phase III clinical trial evaluating ivonescimab monotherapy to pembrolizumab monotherapy in the first-line treatment of patients with metastatic NSCLC whose tumors have high PD-L1 expression (PD-L1 Score > 50%). The study is currently recruiting, with a target enrollment of 780 patients globally. The co-primary endpoints of HARMONi-7 are PFS and OS.

The HARMONi-2 study is being conducted by Akeso in China, where ivonescimab is approved and commercially available for indications in NSCLC. Ivonescimab remains investigational and is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe.

About Ivonescimab

Ivonescimab, known as SMT112 in Summit’s license territories, North America, South America, Europe, the Middle East, Africa, and Japan, and as AK112 outside of Summit’s license territories, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. By design, ivonescimab displays unique cooperative binding to each of its intended targets with multifold higher affinity to PD-1 when in the presence of VEGF.

This design is intended to differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Summit believes ivonescimab’s specifically engineered tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME (Zhong, et al, iScience, 2025). This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of ivonescimab’s design, together with a half-life of 6 to 7 days after the first dose (Zhong, et al, iScience, 2025) and increasing to approximately 10 days at steady state dosing, is to improve upon previously established efficacy thresholds, side effects, and safety profiles associated with prior approved drugs to these targets.

Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently utilized in multiple Phase III clinical trials. Over 4,000 patients have been treated with ivonescimab in clinical studies globally and over 70,000 patients when considering those treated in a commercial setting in China, as noted by Akeso.

There are currently 16 Phase III clinical studies that are either announced, ongoing, or have been completed studying ivonescimab, five of which are Summit-sponsored global studies, one of which is a multiregional study sponsored by a cooperative group, and 10 of which are being or have been conducted in China by Akeso. Summit began its clinical development of ivonescimab in NSCLC, commencing enrollment in 2023 in two multiregional Phase III clinical trials, HARMONi and HARMONi-3. In 2025, Summit began enrolling patients in HARMONi-7. Summit expanded its Phase III clinical development program into colorectal cancer (CRC) in the fourth quarter of 2025 by initiating enrollment in HARMONi-GI3. In 2026, Summit announced initiation of HARMONi-GU1, a Phase II/III study in urothelial carcinoma (bladder cancer) with global clinical trial site activations planned to begin by the fourth quarter of 2026.

HARMONi is a Phase III clinical trial evaluating ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who were previously treated with a third-generation EGFR TKI (e.g., osimertinib). Detailed results of the study were provided in September 2025, and a Biologics License Application (BLA) was submitted to the United States Food and Drug Administration (FDA) for marketing authorization, which the FDA accepted for filing in January 2026; the goal Prescription Drug User Fee Act (PDUFA) date is November 14, 2026.

HARMONi-3 is a Phase III clinical trial evaluating ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic, squamous or non-squamous NSCLC, irrespective of PD-L1 expression. The clinical trial is evaluating the two histologies as individual, separately powered cohorts with independent statistical powering.

HARMONi-7 is a Phase III clinical trial evaluating ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression.

HARMONi-GI3 is a Phase III clinical trial evaluating ivonescimab in combination with chemotherapy compared with bevacizumab plus chemotherapy in patients with first-line unresectable metastatic CRC.

HARMONi-GU1 is a Phase II/III clinical trial evaluating ivonescimab plus the antibody drug conjugate (ADC) enfortumab vedotin (EV) compared to pembrolizumab plus EV as first-line therapy in patients with previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC).

ILLUMINE is a Phase III study being conducted by GORTEC, a cooperative group dedicated to Head and Neck Oncology, in recurrent / metastatic head and neck squamous cell carcinoma (r/m HNSCC). ILLUMINE is a three-arm Phase III clinical trial designed to evaluate ivonescimab monotherapy, as well as ivonescimab in combination with ligufalimab, Akeso’s proprietary anti-CD47 monoclonal antibody, compared to monotherapy pembrolizumab in patients with PD-L1 positive r/m HNSCC.

Five Phase III ivonescimab clinical trials have read out to date, all five with positive data. Four of these five studies are in NSCLC, and one is in biliary tract cancer (BTC). In addition to Summit’s positive HARMONi study, Akeso has had positive read-outs in three single-region (China), randomized Phase III clinical trials in NSCLC, HARMONi-A, HARMONi-2, and HARMONi-6, including a statistically significant overall survival benefit in all three studies. Akeso has also reported a statistically significant OS benefit in the single-region (China), randomized Phase III HARMONi-GI1 trial in advanced BTC.

HARMONi-A was a Phase III clinical trial which evaluated ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with an EGFR TKI.

HARMONi-2 is a Phase III clinical trial evaluating monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression.

HARMONi-6 is a Phase III clinical trial evaluating ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous NSCLC, irrespective of PD-L1 expression.

HARMONi-GI1 is a Phase III clinical trial evaluating ivonescimab in combination with chemotherapy compared with durvalumab plus chemotherapy as a first-line treatment for patients with advanced BTC.

Akeso is actively conducting additional Phase III clinical studies in settings outside of NSCLC and biliary-tract cancer, including triple-negative breast cancer, head and neck squamous cell carcinoma, small cell lung cancer, colorectal cancer, and pancreatic cancer.

Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was initially approved for marketing authorization in China in May 2024.

About Summit Therapeutics Inc.

Summit Therapeutics Inc. is a biopharmaceutical oncology company focused on the discovery, development, and commercialization of patient-, physician-, caregiver- and societal-friendly medicinal therapies intended to improve quality of life, increase potential duration of life, and resolve serious unmet medical needs.

Summit was founded in 2003 and the company’s shares are listed on the Nasdaq Global Market (symbol “SMMT”). Summit is headquartered in Miami, Florida, with additional offices in Palo Alto, California, Princeton, New Jersey, Dublin, Ireland, and Oxford, UK.

For more information, please visit https://www.smmttx.com and follow Summit on X @SMMT_TX.

Summit Forward-Looking Statements

Any statements in this press release about the Company’s future expectations, plans and prospects, including but not limited to, statements about the clinical and preclinical development of the Company’s product candidates, entry into and actions related to the Company’s partnership with Akeso Inc. and other collaborations, the intended use of the net proceeds from the private placements, the Company’s anticipated spending and cash runway, the therapeutic potential of the Company’s product candidates, the potential commercialization of the Company’s product candidates, the timing of initiation, completion and availability of data from clinical trials, the potential submission of applications for marketing approvals, the expected timing of BLA submissions or FDA decisions, potential acquisitions, statements about the previously disclosed At-The-Market equity offering program (“ATM Program”), the expected proceeds and uses thereof, the Company’s estimates regarding stock-based compensation, and other statements containing the words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including the Company’s ability to sell shares of our common stock under the ATM Program, the conditions affecting the capital markets, general economic, industry, or political conditions, including the effects of geopolitical developments, domestic and foreign trade policies, and monetary policies, the results of our evaluation of the underlying data in connection with the development and commercialization activities for ivonescimab, the outcome of discussions with regulatory authorities, including the Food and Drug Administration, the uncertainties inherent in the initiation of future clinical trials, availability and timing of data from ongoing and future clinical trials, the results of such trials, and their success, global public health crises, that may affect timing and status of our clinical trials and operations, whether preliminary results from a clinical trial will be predictive of the final results of that trial or whether results of early clinical trials or preclinical studies will be indicative of the results of later clinical trials, whether business development opportunities to expand the Company’s pipeline of drug candidates, including without limitation, through potential acquisitions of, and/or collaborations with, other entities occur, expectations for regulatory approvals, laws and regulations affecting government contracts and funding awards, availability of funding sufficient for the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements and other factors discussed in the “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections of filings that the Company makes with the Securities and Exchange Commission. Summit defines a “positive study” as a clinical study with one or more prespecified primary endpoints in which one of those endpoints achieves a statistically significant benefit according to the protocol or statistical analysis plan. Any change to our ongoing trials could cause delays, affect our future expenses, and add uncertainty to our commercialization efforts, as well as to affect the likelihood of the successful completion of clinical development of ivonescimab. Accordingly, readers should not place undue reliance on forward-looking statements or information. In addition, any forward-looking statements included in this press release represent the Company’s views only as of the date of this release and should not be relied upon as representing the Company’s views as of any subsequent date. The Company specifically disclaims any obligation to update any forward-looking statements included in this press release.

References:

  1. Xiong A, Wang L, Chen J, Wu L, Liu B, Yao J, et al. Ivonescimab versus pembrolizumab for PD-L1-positive non-small cell lung cancer (HARMONi-2): a randomised, double-blind, phase 3 study in China. Lancet. 2025;405(10481):839-849. doi:10.1016/S0140-6736(24)02722-3.

Summit Therapeutics and the Summit Therapeutics logo are registered trademarks of Summit Therapeutics Inc. and/or its affiliates. Copyright 2026, Summit Therapeutics Inc. All Rights Reserved.

Summit Therapeutics’ Media & Investor Contacts:

Nathan LiaBraaten

Senior Director, Investor Relations

Tracy Jones

Director, Media & Public Relations

[email protected]

[email protected]

KEYWORDS: North America United States South Korea Asia Pacific China Florida

INDUSTRY KEYWORDS: Oncology Health Clinical Trials Research Science Pharmaceutical Biotechnology

MEDIA:

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WIX 10-DAY DEADLINE ALERT: Wix.com Ltd. Investors Alerted to September 22, 2026 Lead Plaintiff Deadline in Securities Class Action Lawsuit

SAN FRANCISCO, Sept. 12, 2026 (GLOBE NEWSWIRE) — Wix.com Ltd. (NASDAQ: WIX) faces a securities class action in the wake of mid-May’s massive 27% drop in the price of the company’s shares after Wix announced its Q1 2026 financial results. Among the disappointments, operating expenses unexpectedly spiked 46% year-over-year leading to questions about the company’s ability to defend its core business.

The case is Yappi v. Wix.com Ltd., et al., No. 26-cv-08852 (N.D. Ill.).

The lawsuit seeks to represent investors who purchased or otherwise acquired Wix securities between February 19, 2025 and May 12, 2026.

National shareholders rights firm Hagens Berman continues its investigation into claims that Wix violated the federal securities laws and urges Wix investors who suffered significant losses to contact the firm now to discuss their rights.

Class Period: Feb. 19, 2025 – May 12, 2026
Lead Plaintiff Deadline: Sept. 22, 2026
Visit:www.hbsslaw.com/wix
Contact the Firm Now:[email protected]
                                       844-916-0895

Wix.com Ltd. (WIX) Securities Class Action:

Global web development platform company Wix faces increasing competitive challenges posed by vibe coding, a software development trend where a person builds apps or websites by giving plain-language instructions to an AI rather than writing code line-by-line.

To confront this challenge, Wix positioned AI initiatives, Base44 and Harmony, as its two-pillar response to the vibe coding trend threatening the company’s core business.

The company has provided numerous assurances to investors, including that “[w]e expect innovation-driven growth to be accompanied by high impact but disciplined investments to fully unlock the market opportunity ahead for both Wix and Base44.” In addition, Wix has emphasized “[e]arly Wix Harmony performance is better than expected, with improved conversion and monetization[,]” and “[t]ogether, Wix Harmony and Base44 open up the world of what’s possible on Wix[.]”

The complaint alleges that Wix made false and misleading statements while failing to disclose that, with respect to its AI product offerings, Wix overstated their competitiveness and performance, understated the costs associated with developing and promoting them and, accordingly, overstated their commercial and financial benefits.

Investors began to learn the truth on May 21, 2025, when Wix provided 2025 revenue guidance falling short of analyst expectation and fueling concerns about the company’s competitiveness. Then, on November 19, 2025, Wix reported its Q3 2025 results indicating rising post-Base44-acquisition costs (AI compute and marketing) were having a material negative impact on its financial results. Each of these triggered sharp selloffs in the price of the stock and triggered analyst downgrades on concerns over core business growth deceleration, increasing costs, and competitive positioning.

Finally, on May 13, 2026, Wix revealed aggressive and front-loaded AI compute expenses for Harmony and Base44. More specifically, the rapid expansion of Base44 and Harmony rollout radically altered Wix’s cost structure primarily through front-loading sales and marketing (“S&M”) expenses. Collectively, the initiatives drove non-GAAP S&M expenses to $190.7 million, a year-over-year 88% increase that caused the company’s non-GAAP operating margin to collapse from 21% during the prior year period to just 5% while sending its quarterly operating expenses up 46% from the prior year period.

During the earnings call that day, management acknowledged that professional development customers were using competing AI tools, the Harmony platform had “holes” and “missing capabilities,” and there had been delays in delivering product updates and innovation to professional developer customers resulting in Wix falling behind their workflows and needs.

The market swiftly reacted that day, scalping over $1.1 billion from Wix’s market capitalization and prompting analysts’ surprise over the magnitude of the margin miss.

“We’re investigating whether Wix may have intentionally understated the adverse effects of its AI initiatives on its operating results,” said Reed Kathrein, the Hagens Berman partner leading the firm’s investigation.

If you invested in Wix and have substantial losses, or have knowledge that may assist the firm’s investigation, submit your losses now »

If you’d like more information and answers to frequently asked questions about the Wix case and the firm’s investigation, read more »

Whistleblowers: Persons with non-public information regarding Wix should consider their options to help in the investigation or take advantage of the SEC Whistleblower program. Under the new program, whistleblowers who provide original information may receive rewards totaling up to 30 percent of any successful recovery made by the SEC. For more information, call Reed Kathrein at 844-916-0895 or email [email protected].

About Hagens Berman

Hagens Berman is a global plaintiffs’ rights complex litigation firm focusing on corporate accountability. The firm is home to a robust practice and represents investors as well as whistleblowers, workers, consumers and others in cases achieving real results for those harmed by corporate negligence and other wrongdoings. Hagens Berman’s team has secured more than $2.9 billion in this area of law. More about the firm and its successes can be found at hbsslaw.com. Follow the firm for updates and news at @ClassActionLaw. 

Attorney Advertising. Prior results do not guarantee a similar outcome in any future case.

Contact: Hagens Berman, Reed Kathrein, 715 Hearst Avenue, Suite 300, Berkeley, CA 94710, 844-916-0895, [email protected]



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PRCT 10-DAY DEADLINE ALERT: PROCEPT BioRobotics Corporation Investors Alerted to September 22, 2026 Lead Plaintiff Deadline in Class Action Lawsuit

SAN FRANCISCO, Sept. 12, 2026 (GLOBE NEWSWIRE) — Hagens Berman Sobol Shapiro LLP alerts investors in PROCEPT BioRobotics Corporation (NASDAQ: PRCT) that a securities class action has been filed after repeated surprise unit handpiece sales underperformance and gradual revelations of excess customer inventory levels driven by repeated, late-quarter, bulk discounts. The lawsuit seeks to represent investors who purchased or otherwise acquired PROCEPT common stock between February 28, 2024 and February 25, 2026.

National shareholders rights firm Hagens Berman is investigating legal claims that PROCEPT and the other Defendants violated the federal securities laws in their communications about sales of the company’s single-use handpiece, a component of its proprietary Aquablation therapy used to treat patients with an enlarged prostate.

The firm encourages investors who suffered substantial losses to submit your losses now. Persons with knowledge who may be able to assist the investigation are invited to contact the firm’s attorneys.

View our latest video summary of the allegations: youtu.be/N5u0rLr0QmA

Class Period: Feb. 28, 2024 – Feb. 25, 2026
Lead Plaintiff Deadline: Sept. 22, 2026
Visit:www.hbsslaw.com/prct
Contact the Firm Now: [email protected]
                                        844-916-0895

PROCEPT BioRobotics (PRCT) Securities Class Action:

The lawsuit alleges that during the Class Period, the defendants withheld crucial information from investors about PROCEPT’s business, operations, and financial condition. Its focus is on the propriety of the company’s statements and omissions related to handpiece sales practices in the U.S., including repeated touting of growth in those sales.

More specifically, the complaint alleges that (unknown to investors) the wrongdoing consisted of company’s utilization of an extensive discount program to incentivize its customers to place bulk orders exceeding customers’ procedures demands, pulling forward sales at the expense of future periods and, thereby, artificially inflating reported unit sales and revenues.

Investors began to learn the truth through a series of partial disclosures, each of which drove the price of PROCEPT shares sharply lower.

On August 6, 2025, PROCEPT announced its Q2 2025 financial results, revealing that the company’s handpiece sales unexpectedly deteriorated, missing consensus estimates by a wide margin.

Then, on November 4, 2025 PROCEPT reported its Q3 2025 results, again missing expected handpiece unit sales. During the corresponding earnings call, management slashed annual handpiece unit sales guidance to allow for the “optimization of field inventory[,]” and said PROCEPT had not “been managing customer inventory[,]” adding that some customers were “probably carrying too much.”

Finally, on February 25, 2026 PROCEPT announced Q4 2025 results. For the first time, the company disclosed the actual number of procedures in the field and revealed that U.S. handpiece sales materially exceeded procedures in each quarter since Q1 2023.

Of concern was that cumulative excess customer inventory of handpieces were over 10,000 units and U.S. handpiece sales sequentially cratered by 30%. Management then said that the company was eliminating its (previously undisclosed) bulk order discount program which was designed to incentivize customers to make large purchases during “the final weeks” of every quarter. The problem was the bulk order discount program essentially ate into future sales as customers already had excess inventories.  

As a result of these events, by February 25, the price of PROCEPT shares had steadily declined by $22.06, or over 48% from the close on August 6, 2025.

“We’re focused on whether PROCEPT may have intentionally pulled-in sales from future quarters to make it seem like the company was meeting expectations and, if so, whether the company had been sufficiently transparent in its investor communications,” said Reed Kathrein, the Hagens Berman partner leading the firm’s investigation.

If you invested in PROCEPT and have substantial losses, or have knowledge that will assist the firm’s investigation, submit your losses now »

If you’d like more information and answers to other frequently asked questions about the PROCEPT case and the firm’s investigation, read more »

Whistleblowers: Persons with non-public information regarding PROCEPT should consider their options to help in the investigation or take advantage of the SEC Whistleblower program. Under the new program, whistleblowers who provide original information may receive rewards totaling up to 30 percent of any successful recovery made by the SEC. For more information, call Reed Kathrein at 844-916-0895 or email [email protected].

About Hagens Berman

Hagens Berman is a global plaintiffs’ rights complex litigation firm focusing on corporate accountability. The firm is home to a robust practice and represents investors as well as whistleblowers, workers, consumers and others in cases achieving real results for those harmed by corporate negligence and other wrongdoings. Hagens Berman’s team has secured more than $2.9 billion in this area of law. More about the firm and its successes can be found at hbsslaw.com. Follow the firm for updates and news at @ClassActionLaw. 

Attorney Advertising. Prior results do not guarantee a similar outcome in any future case.

Contact: Hagens Berman, Reed Kathrein, 715 Hearst Avenue, Suite 300, Berkeley, CA 94710, 844-916-0895, [email protected]



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CCOI 9-DAY DEADLINE ALERT: Cogent Communications Holdings, Inc. Investors Alerted to September 21, 2026 Lead Plaintiff Deadline in Securities Fraud Class Action

SAN FRANCISCO, Sept. 12, 2026 (GLOBE NEWSWIRE) — Hagens Berman Sobol Shapiro LLP —a national plaintiffs’ rights law firm with a premier securities practice group—notifies investors in Cogent Communications Holdings, Inc. (NASDAQ: CCOI) of the upcoming September 21, 2026 lead plaintiff deadline in the ongoing securities class action. This alert follows Cogent’s recent Q2 2026 financial disclosures, which underscore ongoing operational contractions as the class action moves forward.

The firm encourages investors who suffered substantial losses to submit your losses now.  

Q2 2026 Results Highlight Persistent Top-Line Pressures

On Aug. 6, 2026, Cogent reported its financial results for the second quarter of 2026, revealing continued revenue softening across core segments. Service revenue dipped to $235.6 million (representing a sequential decline from Q1 2026 and a year-over-year contraction), accompanied by ongoing double-digit drops in off-net revenue and declining customer connections. These results follow a pattern of balance-sheet adjustments, asset sales, and dividend recalibrations that have drawn heightened scrutiny from the investment community.

Key Case Details:

Class Period: Feb. 29, 2024 – May 1, 2026
Lead Plaintiff Deadline: Sept. 21, 2026
Visit:www.hbsslaw.com/ccoi
Contact the Firm Now: [email protected]
                                        844-916-0895

About the Securities Class Action:

The lawsuit challenges the propriety of Cogent’s disclosures about its optical wavelength “backlog,” assurances that this metric was somehow an indicator of its expected growth and, by extension, its reasonably expected revenue growth and stock’s value.

The complaint alleges that Cogent’s wavelength backlog was an illusory touted measure and unlikely to ever convert to revenue, that large quantities of customers in the backlog were unable or unwilling to accept delivery even if Cogent was in a position to provision the wavelength in a timely manner and that, as a result, the company materially misrepresented customer demand for its optical wavelength services and the nature of its backlog.

Cracks in Cogent’s early Class Period narrative began to emerge on February 27, 2025. That day, Cogent reported disappointing Q4 and FY 2024 financial results and revealed a 20% sequential decline in its backlog and that it removed 1500 orders because many were over one year old. Surprised, the market sent the price of the stock steeply lower.

Then, on May 8, 2025, the company reported disappointing Q1 2025 results and said it had more installation capacity than orders ready to be installed. Management said, “we built a funnel of wavelength opportunities with no defined installation window […] [a]nd as expected, the majority of that funnel fell out.” The market’s reaction was similar to February.

In apparent recognition that investors lost faith in the wavelength backlog story, the company abruptly ceased providing backlog data on February 20, 2026, when it reported Q4 and FY 2025 results. Again, the market sent the price of Cogent shares steeply lower.

Finally, on May 4, 2026, Cogent reported its Q1 2026 results that again disappointed on wavelength revenue and customer connections. Management conceded “[o]n wavelength installs, we have seen a variety of customers pushing out their acceptance[]” and “[w]e actually provisioned more wavelengths in the quarter than we did in the previous quarter, but the customers did not accept them.”

Hagens Berman’s Investigation

“We’re focused on whether Cogent and its management intentionally promoted wavelength backlog and funnel as a way to misrepresent both the company’s actual ability to convert them to earned revenues and the real company-centric wavelength demand,” said Reed Kathrein, the Hagens Berman partner leading the firm’s investigation.

What Can Investors Do?

If you invested in Cogent and have substantial losses, submit your losses now.

If you’d like more information and answers to other frequently asked questions about the Cogent case and the firm’s investigation, read more »

Whistleblowers: Persons with non-public information regarding Cogent should consider their options to help in the investigation or take advantage of the SEC Whistleblower program. Under the new program, whistleblowers who provide original information may receive rewards totaling up to 30 percent of any successful recovery made by the SEC. For more information, call Reed Kathrein at 844-916-0895 or email [email protected].

About Hagens Berman

Hagens Berman is a global plaintiffs’ rights complex litigation firm focusing on corporate accountability. The firm is home to a robust practice and represents investors as well as whistleblowers, workers, consumers and others in cases achieving real results for those harmed by corporate negligence and other wrongdoings. Hagens Berman’s team has secured more than $2.9 billion in this area of law. More about the firm and its successes can be found at hbsslaw.com. Follow the firm for updates and news at @ClassActionLaw. 

Attorney Advertising. Prior results do not guarantee a similar outcome in any future case.

Contact: Hagens Berman, Reed Kathrein, 715 Hearst Avenue, Suite 300, Berkeley, CA 94710, 844-916-0895, [email protected]