Market Newsdesk

BEIJING, May 31, 2026 /PRNewswire/ — iHuman Inc. (NYSE: IH) (“iHuman” or the “Company”), a leading provider of tech-powered, intellectual development products in China, today announced that it has entered into certain asset transfer agreements to acquire the businesses and assets related to two products, All Knowledge (全知识) and Perfect Lingo (万词王) (the “Acquisitions”), for an aggregate consideration of RMB94.0 million, subject to potential two-way price adjustments and contingent earn-out payments.

All Knowledge is an app that focuses on humanities and AI literacy, providing users with AI-powered interactive access to knowledge across history, culture, literature, philosophy, art, and other humanities fields. All Knowledge features a number of systematic learning tools, including spatio-temporal views, historical timelines, and relationship graphs. It has also launched a series of ladder-style learning products, including Elite Youth Tianti, which is among China’s first batch of systematic general knowledge learning programs, Literature and History Tianti, which provides comprehensive and structured learning content for literature and history enthusiasts, and AI Tianti, which is designed to help users better apply, understand, and harness AI.

Perfect Lingo is an AI learning app designed to help users expand their vocabulary, improve pronunciation, and develop comprehensive English learning capabilities through real-life scenarios and video-based learning, extensive dictionaries, AI-powered assessment, intensive training exercises, and pronunciation practice, as well as a personalized AI learning system built around vocabulary learning.

Mr. Michael Yufeng Chi, founder and chairman of iHuman, commented, “We are pleased to announce the acquisition of the businesses and assets related to All Knowledge and Perfect Lingo. The Acquisitions represent not only an important step in expanding our product portfolio, but also a strategically meaningful move for us in the industry. All Knowledge and Perfect Lingo bring strong content, AI technology capabilities, deep understanding of the learning market across all age groups, and proven organizational execution in sales and services. All Knowledge and Perfect Lingo are highly complementary to our existing product ecosystem, and will open up new market opportunities for us. The addition of these products will also help us extend the boundaries of our services and the user groups we reach, while further expanding our product portfolio and AI capabilities, deepening our content offerings, diversifying our product ecosystem, and generating stronger synergies across our products. We believe this initiative will significantly enhance our market competitiveness and unlock substantial potential for future growth.

In addition, on behalf of the board of directors, I am pleased to announce the appointment of Mr. Teng Li from All Knowledge and Perfect Lingo as Co-Chief Executive Officer (Co-CEO) of iHuman, effective upon closing of the transactions. We are also pleased to welcome Ms. Congyu Lin as our new Chief Strategy Officer (CSO) to support the Company’s business development. Prior to joining iHuman, Ms. Congyu Lin held the position of Senior Vice President at Perfect World, and will bring her extensive experience in management and strategic planning to us. Mr. Li and Ms. Lin have each demonstrated outstanding leadership and deep expertise in their respective fields. Their addition will bring fresh energy and strategic vision to iHuman. We believe they will work closely with our existing management team to further drive the Company’s business development, open up broader market opportunities, and create more sustainable growth momentum,” Mr. Chi concluded.

Pursuant to the asset transfer agreements, the Company will conduct acquisition of the businesses and assets related to All Knowledge and Perfect Lingo, for considerations of RMB67.0 million and RMB27.0 million, respectively, subject to potential purchase price adjustments. The purchase prices would be adjusted downward to RMB51.0 million for All Knowledge and RMB21.0 million for Perfect Lingo if certain material adverse events occur. In addition, the sellers may be entitled to contingent earn-out payments of up to RMB29.0 million for All Knowledge and RMB12.0 million for Perfect Lingo in cash, subject to the achievement of certain financial conditions over the next three years. The Company engaged the valuation services of a “Big Four” accounting firm (the “Valuer”) to prepare an independent third-party valuation. The considerations were determined with the assistance of the Valuer. The Acquisitions, which constitute related party transactions due to the common control between the transferors and the Company, have been approved by the board of directors and the audit committee and are subject to customary closing conditions. The appointments of Mr. Teng Li and Ms. Congyu Lin have also been nominated by the Company’s nominating and corporate governance committee and approved by the board of directors.

Safe Harbor Statement

This announcement contains forward-looking statements. These statements are made under the “safe harbor” provisions of the United States Private Securities Litigation Reform Act of 1995. These forward-looking statements can be identified by terminology such as “will,” “expects,” “anticipates,” “future,” “intends,” “plans,” “believes,” “estimates” and similar statements. Statements that are not historical facts, including statements about iHuman’s beliefs and expectations, are forward-looking statements. Among other things, the description of the management’s quotations in this announcement contains forward-looking statements. iHuman may also make written or oral forward-looking statements in its periodic reports to the U.S. Securities and Exchange Commission (the “SEC”), in its annual report to shareholders, in press releases and other written materials, and in oral statements made by its officers, directors or employees to third parties. Forward-looking statements involve inherent risks and uncertainties. A number of factors could cause actual results to differ materially from those contained in any forward-looking statement, including but not limited to the following: iHuman’s growth strategies; its future business development, financial condition and results of operations; its ability to continue to attract and retain users, convert non-paying users into paying users and increase the spending of paying users, the trends in, and size of, the market in which iHuman operates; its expectations regarding demand for, and market acceptance of, its products and services; its expectations regarding its relationships with business partners; general economic and business conditions; regulatory environment; and assumptions underlying or related to any of the foregoing. Further information regarding these and other risks is included in iHuman’s filings with the SEC. All information provided in this press release is as of the date of this press release, and iHuman does not undertake any obligation to update any forward-looking statement, except as required under applicable law.

About iHuman Inc.

 iHuman Inc. is a leading provider of tech-powered, intellectual development products in China that is committed to making the child-upbringing experience easier for parents and transforming intellectual development into a fun journey for children. Benefiting from a deep legacy that combines nearly three decades of experience in the parenthood industry, superior original content, advanced high-tech innovation DNA and research & development capabilities with cutting-edge technologies, iHuman empowers parents with tools to make the child-upbringing experience more efficient. iHuman’s unique, fun and interactive product offerings stimulate children’s natural curiosity and exploration. The Company’s comprehensive suite of innovative and high-quality products include self-directed apps, interactive content and smart devices that cover a broad variety of areas to develop children’s abilities in speaking, critical thinking, independent reading and creativity. Leveraging advanced technological capabilities, including 3D engines, AI/AR functionality, and big data analysis on children’s behavior & psychology, iHuman believes it will continue to provide superior experience that is efficient and relieving for parents, and effective and fun for children, in China and all over the world, through its integrated suite of tech-powered, intellectual development products.

For investor and media enquiries, please contact:

iHuman Inc.
Mr. Justin Zhang
Investor Relations Director
Phone: +86-10-5780-6606
E-mail: [email protected]

Christensen Advisory
Ms. Alice Li
Phone: +86-10-5900-1548
E-mail: [email protected]

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SOURCE iHuman Inc.

CALGARY, AB, May 31, 2026 /PRNewswire/ – Canadian Pacific Kansas City (TSX: CP) (NYSE: CP) (CPKC) today said it has implemented contingency plans to maintain railway operations across Canada following the International Brotherhood of Electrical Worker (IBEW) Canadian Signals and Communications System Council No. 11’s rejection of CPKC’s latest contract offers. 

The IBEW, representing approximately 300 Signals & Communications employees in Canada, launched a strike at 08:00 MDT Sunday, May 31. Safe and efficient rail service has continued. 

After spending months bargaining in good faith, CPKC is disappointed that a work stoppage could not be prevented. CPKC has presented a fair and balanced proposal with wage and benefit increases consistent with collective agreements currently in place with all our other unions across Canada. 

We continue to encourage IBEW to end its strike and accept binding arbitration.

CPKC has an excellent track record of successful collective bargaining with bargaining units across North America. We remain hopeful that a resolution can be reached quickly. 

About CPKC
With its global headquarters in Calgary, Alta., Canada, CPKC is the first and only single-line transnational railway linking Canada, the United States and México, with unrivaled access to major ports from Vancouver to Atlantic Canada to the Gulf Coast to Lázaro Cárdenas, México. Stretching approximately 20,000 route miles and employing approximately 20,000 railroaders, CPKC provides North American customers unparalleled rail service and network reach to key markets across the continent. CPKC is growing with its customers, offering a suite of freight transportation services, logistics solutions and supply chain expertise. Visit cpkcr.com to learn more about the rail advantages of CPKC. CP-IR

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SOURCE CPKC

• More than one-third of responders with previously treated disease achieved complete responses, with median duration of response not yet reached, as reported in new Journal of Clinical Oncology publication 
• RYBREVANT FASPRO™, an EGFR– and MET-targeting dual inhibitor, is the first and only subcutaneous therapy being evaluated in this setting 
• Johnson & Johnson submitted a supplemental
  Biologics License Application to U.S. FDA seeking approval for this indication 

CHICAGO, May 31, 2026 /PRNewswire/ — Johnson & Johnson (NYSE: JNJ) today announced pivotal results from the Phase 1b/2 OrigAMI-4 study showing that subcutaneous amivantamab and hyaluronidase-lpuj delivered durable responses in patients with advanced head and neck squamous cell carcinoma previously treated with immunotherapy and chemotherapy. Confirmed overall response rate was 42 percent, with more than one-third of responders achieving complete responses. Median duration of response was not yet reached, with a median follow up of 11.8 months.¹ These data were featured in an oral session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #6008) and simultaneously published in the Journal of Clinical Oncology (JCO).² Together, with additional data presented in lung and colorectal cancers, these findings further demonstrate the expanding role of the amivantamab portfolio across tumor types.

A supplemental Biologics License Application (sBLA) seeking approval for subcutaneous amivantamab in head and neck cancer has been submitted to the U.S. Food and Drug Administration (FDA), following Breakthrough Therapy Designation.

High unmet need remains in advanced head and neck cancer

Head and neck squamous cell carcinoma is an aggressive disease that can significantly affect quality of life, with symptoms such as pain and difficulty swallowing that can make it hard to eat, speak and maintain proper nutrition.^3,4 Certain forms of head and neck cancer, including tumors of the mouth, voice box and parts of the throat, are among the most difficult to treat, and are associated with poorer outcomes and persistent unmet need.⁵ Across head and neck cancers, up to half of patients will experience recurrence or metastatic disease, even when treated at an early stage.³ Once the disease becomes recurrent or metastatic, five-year survival is approximately 15 percent.⁶ For patients who receive additional treatment, current options provide limited benefit with response rates rarely exceeding 24 percent, and few patients achieve a complete response.^7,8

Dual-targeting mechanism helps address tumor growth and resistance

Subcutaneous amivantamab is designed to dual target both epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET), two pathways associated with tumor growth and resistance, while engaging the immune system.⁹

“Patients with recurrent or metastatic head and neck cancer who have already been treated with immunotherapy and chemotherapy face very poor outcomes,” said Barbara Burtness, M.D.,* medical oncologist and professor of medicine at Yale Cancer Center in New Haven, Connecticut. “The high response seen with subcutaneous amivantamab on its own, including more than one-third of responders achieving complete responses, and the durability of those responses, suggests it has the potential to meaningfully improve expectations for these patients.”

Detailed OrigAMI-4 study results

Cohort 1 of the OrigAMI-4 study evaluated subcutaneous amivantamab monotherapy in 102 patients with recurrent or metastatic head and neck cancer who had previously received immunotherapy and platinum-based chemotherapy, excluding patients with human papillomavirus (HPV)-positive oropharyngeal cancer. Patients received treatment every three weeks following an initial loading dose. The primary endpoint was overall response rate, as assessed by local investigators per protocol. Responses were confirmed via blinded independent central review (BICR).¹

Based on BICR, confirmed overall response rate was 42 percent (95 percent confidence interval [CI], 32-52), including complete responses in more than one-third of responders (15 percent) and a 27 percent partial response rate. Clinical benefit rate was 63 percent (95 percent CI, 53-72), and median time to first response was 6.6 weeks (range, 5.6-36.9). At the time of analysis (median follow-up of 11.8 months), median duration of response had not yet been reached among confirmed responders, demonstrating notable durability. Median progression-free survival and overall survival were 6.8 months and 12.5 months, respectively.¹

The safety profile of subcutaneous amivantamab monotherapy was consistent with prior reports, with no new safety signals identified. Most treatment-related adverse events were Grade 1 or 2 (mild to moderate) and associated with EGFR or MET inhibition. The most common on-target adverse events included hypoalbuminemia (50 percent), rash (37 percent), paronychia (34 percent) and dermatitis acneiform (34 percent). Administration-related reactions occurred in 15 percent of patients, with no Grade 3 or higher events reported. Treatment-related discontinuations remained low at eight percent.¹

“Progress has been limited for patients with recurrent and metastatic head and neck cancer, highlighting the need for differentiated approaches that can address the disease more comprehensively,” said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson. “Subcutaneous amivantamab is the only therapy of its kind being studied in this disease, targeting both EGFR and MET while engaging the immune system. The encouraging responses we’re seeing in OrigAMI-4, along with a well-established and manageable safety profile, underscore the potential of this approach and move us closer to delivering a fast, convenient treatment option.”

Ongoing study of RYBREVANT FASPRO
™
 in head and neck cancer

A trial-in-progress update from the Phase 3 OrigAMI-5 study (NCT07276399) was also shared at ASCO 2026 (Abstract #583a). The study is evaluating subcutaneous amivantamab in combination with carboplatin and pembrolizumab as a first-line treatment for patients with recurrent or metastatic head and neck cancer, with the goal of improving outcomes in the first-line setting.¹⁰

RYBREVANT FASPRO™ is already approved in more than 40 countries, including the United States, Europe, Japan, and other markets, as a subcutaneous treatment for patients with EGFR-mutated non-small cell lung cancer.¹¹

About the OrigAMI-4 Study

OrigAMI-4 (NCT06385080) is an open-label Phase 1b/2 study evaluating RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The study includes five cohorts exploring RYBREVANT FASPRO™ across different treatment settings and regimens.

Cohort 1 evaluated RYBREVANT FASPRO™ as monotherapy in patients with R/M HNSCC who had received prior platinum-based chemotherapy and PD-1/PD-L1 immunotherapy. Patients with HPV-positive oropharyngeal squamous cell carcinoma were excluded, as well as those with prior anti-EGFR therapy.

RYBREVANT FASPRO™ was administered on a weekly schedule during the initial treatment period followed by dosing every three weeks (Q3W), with weight-based dosing adjustments. The primary endpoint across cohorts is overall response rate (ORR), as assessed by investigators, using RECIST v1.1.^†12

About Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the most common form of head and neck cancer, a group of cancers that arise in the mouth, throat, voice box, sinuses, nasal cavity, and salivary glands.¹³ It represents approximately 4.5 percent of all cancers worldwide and is the seventh most common cancer globally.¹³ Major risk factors include tobacco and alcohol use, as well as infection with high-risk human papillomavirus (HPV).¹³ Approximately 80 percent of recurrent or metastatic HNSCC are not driven by HPV, and are typically associated with poorer prognosis and reduced response to treatment.^{13, 14} Despite advances in surgery, radiation, chemotherapy, and immunotherapy, many patients ultimately progress to advanced, recurrent or metastatic disease.^15,16

About RYBREVANT FASPRO™ and RYBREVANT^®

RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) received U.S. FDA approval in December 2025 and is approved in multiple markets worldwide for the treatment of adults with EGFR-mutated non-small cell lung cancer (NSCLC), including those with exon 19 deletions, exon 21 L858R substitution mutations, and exon 20 insertion mutations. It is the only subcutaneous therapy approved in these populations and can be used as monotherapy or in combination with LAZCLUZE^® (lazertinib) or chemotherapy in the front- and second-line settings, offering convenient monthly^‡ or bi-weekly dosing. RYBREVANT FASPRO™ is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE^® drug delivery technology.

RYBREVANT^® (amivantamab-vmjw), administered intravenously, received U.S. FDA approval in March 2024 and is approved for the same indications as RYBREVANT FASPRO™ across multiple markets. RYBREVANT^® is a first-in-class, fully human bispecific antibody targeting EGFR and MET, designed to inhibit tumor growth while engaging the immune system.

The effectiveness of RYBREVANT FASPRO™ is supported by the established clinical profile of RYBREVANT^®, including data from multiple Phase 3 studies such as MARIPOSA, which demonstrated improvements in progression-free and overall survival when used in combination with LAZCLUZE^® in first-line advanced EGFR-mutated NSCLC.

The National Comprehensive Cancer Network^® (NCCN^®) Clinical Practice Guidelines in Oncology (NCCN Guidelines^®)^§17 include amivantamab-vmjw (RYBREVANT^®) across its FDA-approved treatment settings, including as a Category 1 preferred option in combination with lazertinib (LAZCLUZE^®) for first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations. Subcutaneous amivantamab and hyaluronidase-lpuj (RYBREVANT FASPRO™) may be substituted for IV amivantamab-vmjw (RYBREVANT^®) where appropriate. See the latest NCCN Guidelines^® for NSCLC for complete information. ^{|| ¶}

The NCCN Guidelines for Central Nervous System Cancers also include amivantamab (RYBREVANT^®)-based regimens, including in combination with lazertinib (LAZCLUZE^®), as the only NCCN-preferred combination options for patients with EGFR-mutated NSCLC and brain metastases. ^{|| ¶}

Beyond NSCLC, RYBREVANT-based therapies are being investigated across other solid tumors, including head and neck and colorectal cancers.

The legal manufacturer for RYBREVANT FASPRO™ and RYBREVANT^® is Janssen Biotech, Inc. For more information, visit www.rybrevanthcp.com

INDICATIONS

RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) and RYBREVANT^® (amivantamab-vmjw) are indicated:

• in combination with LAZCLUZE (lazertinib) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.
• in combination with carboplatin and pemetrexed for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor.
• in combination with carboplatin and pemetrexed for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test.
• as a single agent for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA approved test, whose disease has progressed on or after platinum-based chemotherapy.

IMPORTANT SAFETY INFORMATION FOR RYBREVANT FASPRO™ AND RYBREVANT^® 
10
,18

CONTRAINDICATIONS

RYBREVANT FASPRO™ is contraindicated in patients with known hypersensitivity to hyaluronidase or to any of its excipients.

WARNINGS AND PRECAUTIONS

Hypersensitivity and Administration-Related Reactions with RYBREVANT FASPRO™

RYBREVANT FASPRO™ can cause hypersensitivity and administration-related reactions (ARR); signs and symptoms of ARR include dyspnea, flushing, fever, chills, chest discomfort, hypotension, and vomiting. The median time to ARR onset is approximately 2 hours.

RYBREVANT FASPRO™ with LAZCLUZE^®

In PALOMA-3 (n=206), all Grade ARR occurred in 13% of patients, including 0.5% Grade 3. Of the patients who experienced ARR, 89% occurred with the initial dose (Week 1, Day 1).

Premedicate with antihistamines, antipyretics, and glucocorticoids and administer RYBREVANT FASPRO™ as recommended. Monitor patients for any signs and symptoms of administration-related reactions during injection in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt RYBREVANT FASPRO™ injection if ARR is suspected. Resume treatment upon resolution of symptoms or permanently discontinue RYBREVANT FASPRO™ based on severity.

Infusion-Related Reactions with RYBREVANT^®

RYBREVANT^® can cause infusion-related reactions (IRR) including anaphylaxis; signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting. The median time to IRR onset is approximately 1 hour.

RYBREVANT
^®
 with LAZCLUZE
^®

In MARIPOSA (n=421), IRRs occurred in 63% of patients, including Grade 3 in 5% and Grade 4 in 1% of patients. IRR-related infusion modifications occurred in 54%, dose reduction in 0.7%, and permanent discontinuation of RYBREVANT^® in 4.5% of patients.

RYBREVANT
^®
 with Carboplatin and Pemetrexed

Based on the pooled safety population (n=281), IRRs occurred in 50% of patients including Grade 3 (3.2%) adverse reactions. IRR-related infusion modifications occurred in 46%, and permanent discontinuation of RYBREVANT^® in 2.8% of patients.

RYBREVANT
^®
 as a Single Agent

In CHRYSALIS (n=302), IRRs occurred in 66% of patients. IRRs occurred in 65% of patients on Week 1 Day 1, 3.4% on Day 2 infusion, 0.4% with Week 2 infusion, and were cumulatively 1.1% with subsequent infusions. 97% were Grade 1-2, 2.2% were Grade 3, and 0.4% were Grade 4. The median time to onset was 1 hour (range: 0.1 to 18 hours) after start of infusion. IRR-related infusion modifications occurred in 62%, and permanent discontinuation of RYBREVANT^® in 1.3% of patients.

Premedicate with antihistamines, antipyretics, and glucocorticoids and infuse RYBREVANT^® as recommended. Administer RYBREVANT^® via a peripheral line on Week 1 and Week 2 to reduce the risk of IRRs. Monitor patients for signs and symptoms of IRRs in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT^® based on severity. If an anaphylactic reaction occurs, permanently discontinue RYBREVANT^®.

Interstitial Lung Disease/Pneumonitis

RYBREVANT FASPRO™ and RYBREVANT^® can cause severe and fatal interstitial lung disease (ILD)/pneumonitis.

RYBREVANT FASPRO™ with LAZCLUZE^®

In PALOMA-3, ILD/pneumonitis occurred in 6% of patients, including Grade 3 in 1%, Grade 4 in 1.5%, and fatal cases in 1.9% of patients. 5% of patients permanently discontinued RYBREVANT FASPRO™ and LAZCLUZE^® due to ILD/pneumonitis.

RYBREVANT
^®
 with LAZCLUZE
^®

In MARIPOSA, ILD/pneumonitis occurred in 3.1% of patients, including Grade 3 in 1.0% and Grade 4 in 0.2% of patients. There was one fatal case of ILD/pneumonitis and 2.9% of patients permanently discontinued RYBREVANT^® and LAZCLUZE^® due to ILD/pneumonitis.

RYBREVANT
^®
 with Carboplatin and Pemetrexed

Based on the pooled safety population, ILD/pneumonitis occurred in 2.1% of patients with 1.8% of patients experiencing Grade 3 ILD/pneumonitis. 2.1% discontinued RYBREVANT^® due to ILD/pneumonitis.

RYBREVANT
^®
 as a Single Agent

In CHRYSALIS, ILD/pneumonitis occurred in 3.3% of patients, with 0.7% of patients experiencing Grade 3 ILD/pneumonitis. Three patients (1%) permanently discontinued RYBREVANT^® due to ILD/pneumonitis.

Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold RYBREVANT FASPRO™ or RYBREVANT^® and LAZCLUZE^® (when applicable) in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.

Venous Thromboembolic (VTE) Events with Concomitant Use with LAZCLUZE^®

RYBREVANT FASPRO™ and RYBREVANT^® in combination with LAZCLUZE^® can cause serious and fatal venous thromboembolic (VTE) events, including deep vein thrombosis and pulmonary embolism. Without prophylactic anticoagulation, the majority of these events occurred during the first four months of treatment.

RYBREVANT FASPRO™ with LAZCLUZE^®

In PALOMA-3 (n=206), all Grade VTE occurred in 11% of patients and 1.5% were Grade 3. 80% (n=164) of patients received prophylactic anticoagulation at study entry, with an all Grade VTE incidence of 7%. In patients who did not receive prophylactic anticoagulation (n=42), all Grade VTE occurred in 17% of patients. In total, 0.5% of patients had VTE leading to dose reductions of RYBREVANT FASPRO™ and no patients required permanent discontinuation. The median time to onset of VTEs was 95 days (range: 17 to 390).

RYBREVANT^® with LAZCLUZE
^®

In MARIPOSA (n=421), VTEs occurred in 36% of patients including Grade 3 in 10% and Grade 4 in 0.5% of patients. On-study VTEs occurred in 1.2% of patients (n=5) while receiving anticoagulation therapy. There were two fatal cases of VTE (0.5%), 9% of patients had VTE leading to dose interruptions of RYBREVANT^®, and 7% of patients had VTE leading to dose interruptions of LAZCLUZE^®; 1% of patients had VTE leading to dose reductions of RYBREVANT^®, and 0.5% of patients had VTE leading to dose reductions of LAZCLUZE^®; 3.1% of patients had VTE leading to permanent discontinuation of RYBREVANT^®, and 1.9% of patients had VTE leading to permanent discontinuation of LAZCLUZE^®. The median time to onset of VTEs was 84 days (range: 6 to 777).

Administer prophylactic anticoagulation for the first four months of treatment. The use of Vitamin K antagonists is not recommended.

Monitor for signs and symptoms of VTE events and treat as medically appropriate. Withhold RYBREVANT FASPRO™ or RYBREVANT^® and LAZCLUZE^® based on severity. Once anticoagulant treatment has been initiated, resume RYBREVANT FASPRO™ or RYBREVANT^® and LAZCLUZE^® at the same dose level at the discretion of the healthcare provider. In the event of VTE recurrence despite therapeutic anticoagulation, permanently discontinue RYBREVANT FASPRO™ or RYBREVANT^®. Treatment can continue with LAZCLUZE^® at the same dose level at the discretion of the healthcare provider. Refer to the LAZCLUZE^® Prescribing Information for recommended LAZCLUZE^® dosage modification.

Dermatologic Adverse Reactions

RYBREVANT FASPRO™ and RYBREVANT^® can cause severe rash including toxic epidermal necrolysis (TEN), dermatitis acneiform, pruritus and dry skin.

RYBREVANT FASPRO™ with LAZCLUZE^®

In PALOMA-3, rash occurred in 80% of patients, including Grade 3 in 17% and Grade 4 in 0.5% of patients. Rash leading to dose reduction occurred in 11% of patients, and RYBREVANT FASPRO™ was permanently discontinued due to rash in 1.5% of patients.

RYBREVANT
^®
 with LAZCLUZE
^®

In MARIPOSA, rash occurred in 86% of patients, including Grade 3 in 26% of patients. The median time to onset of rash was 14 days (range: 1 to 556 days). Rash leading to dose interruptions occurred in 37% of patients for RYBREVANT^® and 30% for LAZCLUZE^®, rash leading to dose reductions occurred in 23% of patients for RYBREVANT^® and 19% for LAZCLUZE^®, and rash leading to permanent discontinuation occurred in 5% of patients for RYBREVANT^® and 1.7% for LAZCLUZE^®.

RYBREVANT
^®
 with Carboplatin and Pemetrexed

Based on the pooled safety population, rash occurred in 82% of patients, including Grade 3 (15%) adverse reactions. Rash leading to dose reductions occurred in 14% of patients, and 2.5% permanently discontinued RYBREVANT^® and 3.1% discontinued pemetrexed.

RYBREVANT
^®
 as a Single Agent

In CHRYSALIS, rash occurred in 74% of patients, including Grade 3 in 3.3% of patients. The median time to onset of rash was 14 days (range: 1 to 276 days). Rash leading to dose reduction occurred in 5% and permanent discontinuation due to rash occurred in 0.7% of patients. Toxic epidermal necrolysis occurred in one patient (0.3%). 

When initiating treatment with RYBREVANT FASPRO or RYBREVANT and LAZCLUZE, prophylactic and concomitant medications are recommended to reduce the risk and severity of dermatologic adverse reactions. Instruct patients to limit sun exposure during and for 2 months after treatment. Advise patients to wear protective clothing and use broad spectrum UVA/UVB sunscreen.

If skin reactions develop, administer supportive care including topical corticosteroids and topical and/or oral antibiotics. For Grade 3 reactions, add oral steroids and consider dermatologic consultation. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. For patients receiving RYBREVANT FASPRO™ or RYBREVANT^® in combination with LAZCLUZE^®, withhold, reduce the dose, or permanently discontinue both drugs based on severity. For patients receiving RYBREVANT FASPRO™ or RYBREVANT^® as a single agent or in combination with carboplatin and pemetrexed, withhold, dose reduce or permanently discontinue RYBREVANT FASPRO™ or RYBREVANT^® based on severity.

Hepatotoxicity

LAZCLUZE^® in combination with amivantamab can cause severe hepatotoxicity (including increased ALT and AST).

RYBREVANT^® with LAZCLUZE^®

In MARIPOSA, based on adverse reaction data, hepatotoxicity occurred in 49% of patients treated with LAZCLUZE^®, including Grade 3 in 9.3% of patients and Grade 4 in 0.5%. LAZCLUZE^® was interrupted for an adverse reaction of hepatotoxicity in 8% of patients, the dose was reduced in 1.4% and permanently discontinued in 0.2%.

Perform liver function tests (including ALT, AST, and total bilirubin) before initiation of LAZCLUZE^® and during treatment, as clinically indicated. Withhold, reduce the dose, or permanently discontinue LAZCLUZE^® and amivantamab based on severity.

Ocular Toxicity

RYBREVANT FASPRO™ and RYBREVANT^® can cause ocular toxicity including keratitis, blepharitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, eye pruritus and uveitis.

RYBREVANT FASPRO™ with LAZCLUZE^®

In PALOMA-3, all Grade ocular toxicity occurred in 13% of patients, including 0.5% Grade 3.

RYBREVANT
^®
 with LAZCLUZE
^®

In MARIPOSA, ocular toxicity occurred in 16%, including Grade 3 or 4 ocular toxicity in 0.7% of patients.

RYBREVANT
^®
 with Carboplatin and Pemetrexed

Based on the pooled safety population, ocular toxicity occurred in 16% of patients. All events were Grade 1 or 2.

RYBREVANT
^®
 as a Single Agent

In CHRYSALIS, keratitis occurred in 0.7% and uveitis occurred in 0.3% of patients. All events were Grade 1-2.

Promptly refer patients presenting with new or worsening eye symptoms to an ophthalmologist. Withhold, dose reduce or permanently discontinue RYBREVANT FASPRO™ or RYBREVANT^® and continue LAZCLUZE^® based on severity.

Embryo-Fetal Toxicity

Based on animal models, RYBREVANT FASPRO™, RYBREVANT^® and LAZCLUZE^® can cause fetal harm when administered to a pregnant woman. Verify pregnancy status of females of reproductive potential prior to initiating RYBREVANT FASPRO™ and RYBREVANT^®. Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise patients of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of RYBREVANT FASPRO™ or RYBREVANT^®, and for 3 weeks after the last dose of LAZCLUZE^®.

ADVERSE REACTIONS

RYBREVANT FASPRO™ withLAZCLUZE^®

In PALOMA-3 (n=206), the most common adverse reactions (≥20%) were rash (80%), nail toxicity (58%), musculoskeletal pain (50%), fatigue (37%), stomatitis (36%), edema (34%), nausea (30%), diarrhea (22%), vomiting (22%), constipation (22%), decreased appetite (22%), and headache (21%). The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocyte count (6%), decreased sodium (5%), decreased potassium (5%), decreased albumin (4.9%), increased alanine aminotransferase (3.4%), decreased platelet count (2.4%), increased aspartate aminotransferase (2%), increased gamma-glutamyl transferase (2%), and decreased hemoglobin (2%).

Serious adverse reactions occurred in 33% of patients, with those occurring in ≥2% of patients including ILD/pneumonitis (6%); and pneumonia, VTE and fatigue (2.4% each). Death due to adverse reactions occurred in 5% of patients treated with RYBREVANT FASPRO™, including ILD/pneumonitis (1.9%), pneumonia (1.5%), and respiratory failure and sudden death (1% each).

RYBREVANT
^® withLAZCLUZE^®

In MARIPOSA (n=421), the most common adverse reactions (ARs) (≥20%) were rash (86%), nail toxicity (71%), infusion-related reactions (IRRs) (RYBREVANT^®) (63%), musculoskeletal pain (47%), stomatitis (43%), edema (43%), VTE (36%), paresthesia (35%), fatigue (32%), diarrhea (31%), constipation (29%), COVID-19 (26%), hemorrhage (25%), dry skin (25%), decreased appetite (24%), pruritus (24%), and nausea (21%). The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased albumin (8%), decreased sodium (7%), increased ALT (7%), decreased potassium (5%), decreased hemoglobin (3.8%), increased AST (3.8%), increased GGT (2.6%), and increased magnesium (2.6%).

Serious ARs occurred in 49% of patients, with those occurring in ≥2% of patients including VTE (11%), pneumonia (4%), ILD/pneumonitis and rash (2.9% each), COVID-19 (2.4%), and pleural effusion and IRRs (RYBREVANT^®) (2.1% each). Fatal ARs occurred in 7% of patients due to death not otherwise specified (1.2%); sepsis and respiratory failure (1% each); pneumonia, myocardial infarction, and sudden death (0.7% each); cerebral infarction, pulmonary embolism (PE), and COVID-19 infection (0.5% each); and ILD/pneumonitis, acute respiratory distress syndrome (ARDS), and cardiopulmonary arrest (0.2% each).

RYBREVANT
^®
 with Carboplatin and Pemetrexed

In MARIPOSA-2 (n=130), the most common ARs (≥20%) were rash (72%), IRRs (59%), fatigue (51%), nail toxicity (45%), nausea (45%), constipation (39%), edema (36%), stomatitis (35%), decreased appetite (31%), musculoskeletal pain (30%), vomiting (25%), and COVID-19 (21%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased neutrophils (49%), decreased white blood cells (42%), decreased lymphocytes (28%), decreased platelets (17%), decreased hemoglobin (12%), decreased potassium (11%), decreased sodium (11%), increased alanine aminotransferase (3.9%), decreased albumin (3.8%), and increased gamma-glutamyl transferase (3.1%).

In MARIPOSA-2, serious ARs occurred in 32% of patients, with those occurring in >2% of patients including dyspnea (3.1%), thrombocytopenia (3.1%), sepsis (2.3%), and PE (2.3%). Fatal ARs occurred in 2.3% of patients; these included respiratory failure, sepsis, and ventricular fibrillation (0.8% each).

In PAPILLON (n=151), the most common ARs (≥20%) were rash (90%), nail toxicity (62%), stomatitis (43%), IRRs (42%), fatigue (42%), edema (40%), constipation (40%), decreased appetite (36%), nausea (36%), COVID-19 (24%), diarrhea (21%), and vomiting (21%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased albumin (7%), increased alanine aminotransferase (4%), increased gamma-glutamyl transferase (4%), decreased sodium (7%), decreased potassium (11%), decreased magnesium (2%), and decreases in white blood cells (17%), hemoglobin (11%), neutrophils (36%), platelets (10%), and lymphocytes (11%).

In PAPILLON, serious ARs occurred in 37% of patients, with those occurring in ≥2% of patients including rash, pneumonia, ILD, PE, vomiting, and COVID-19. Fatal adverse reactions occurred in 7 patients (4.6%) due to pneumonia, cerebrovascular accident, cardio-respiratory arrest, COVID-19, sepsis, and death not otherwise specified.

RYBREVANT
^®
 as a Single Agent

In CHRYSALIS (n=129), the most common ARs (≥20%) were rash (84%), IRR (64%), paronychia (50%), musculoskeletal pain (47%), dyspnea (37%), nausea (36%), fatigue (33%), edema (27%), stomatitis (26%), cough (25%), constipation (23%), and vomiting (22%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased lymphocytes (8%), decreased albumin (8%), decreased phosphate (8%), decreased potassium (6%), increased alkaline phosphatase (4.8%), increased glucose (4%), increased gamma-glutamyl transferase (4%), and decreased sodium (4%).

Serious ARs occurred in 30% of patients, with those occurring in ≥2% of patients including PE, pneumonitis/ILD, dyspnea, musculoskeletal pain, pneumonia, and muscular weakness. Fatal adverse reactions occurred in 2 patients (1.5%) due to pneumonia and 1 patient (0.8%) due to sudden death.

LAZCLUZE^® DRUG INTERACTIONS

Avoid concomitant use of LAZCLUZE^® with strong and moderate CYP3A4 inducers. Consider an alternate concomitant medication with no potential to induce CYP3A4.

Monitor for adverse reactions associated with a CYP3A4 or BCRP substrate where minimal concentration changes may lead to serious adverse reactions, as recommended in the approved product labeling for the CYP3A4 or BCRP substrate.

Please see full Prescribing Information for

RYBREVANT FASPRO™

,

RYBREVANT^®

 and

LAZCLUZE^®

.

cp-491009v2

About Johnson & Johnson

At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.innovativemedicine.jnj.com. Follow us at @JNJInnovMed.

Cautions Concerning Forward-Looking Statements

This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of RYBREVANT^®-based regimens. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s most recent Annual Report on Form 10-K, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com, www.investor.jnj.com or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments.

*Barbara Burtness, M.D. has served as a consultant to Johnson & Johnson; she has not been paid for any media work. 

^† RECIST (version 1.1) refers to Response Evaluation Criteria in Solid Tumors, which is a standard way to measure how well solid tumors respond to treatment and is based on whether tumors shrink, stay the same or get bigger.

^‡ Once monthly after weekly injections from weeks 1-4.

^§ The NCCN content does not constitute medical advice and should not be used in place of seeking professional medical advice, diagnosis or treatment by licensed practitioners. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

^|| See the NCCN Guidelines for detailed recommendations, including other treatment options.

^¶ The NCCN Guidelines for NSCLC provide recommendations for certain individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories.

¹ Burtness B, et al. Amivantamab in recurrent/metastatic head & neck squamous cell cancer after disease progression on immune checkpoint inhibitor and chemotherapy. Pivotal results from the phase 1b/2 OrigAMI-4 study. Presented at: The 2026 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31, 2026; Chicago, Illinois.
² Burtness B, et al. Amivantamab in recurrent/metastatic HNSCC after checkpoint inhibitor and chemotherapy: pivotal results from the phase 1b/2 OrigAMI-4 study. Epub May 31, 2026. doi:10.1200/JCO-26-01042.
³ Zebralla V, Wichmann G, Pirlich M, et al. Dysphagia, voice problems, and pain in head and neck cancer patients. Eur Arch Otorhinolaryngol. 2021;278(10):3985-3994. doi:10.1007/s00405-020-06584-6
⁴ Nissi L, et al. Recurrence of head and neck squamous cell carcinoma in relation to high-risk treatment volume. Clin Transl Radiat Oncol. 2021;27:139-146. doi:10.1016/j.ctro.2021.01.013
⁵ Dunn LA, Ho AL, Pfister DG. Head and neck cancer: a review. JAMA. 2026;335(6):531-541. doi:10.1001/jama.2025.21733
⁶ Soulieres D, et al. LBA48 BURAN: A phase III study of buparlisib (BUP) plus paclitaxel (PAC) in patients with PD-1(PD-L1)-pretreated recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Ann Oncol. 2025;36:S1707.
⁷ Fayette J, et al. INTERLINK-1: A Phase III, randomized, placebo-controlled study of monalizumab plus cetuximab in recurrent/metastatic head and neck squamous cell carcinoma. Clin Cancer Res. 2025;31(13):2617-2627. doi:10.1158/1078-0432.CCR-25-0073
⁸ Große-Thie C, Maletzki C, Junghanss C, Schmidt K. Long-term survivor of metastatic squamous-cell head and neck carcinoma with occult primary after cetuximab-based chemotherapy: A case report. World J Clin Cases. 2021;9(24):7092-7098. doi:10.12998/wjcc.v9.i24.7092
⁹ Harrington KJ, Rosenberg AJ, Yang MH, et al. Subcutaneous amivantamab in recurrent/metastatic head and neck squamous cell cancer after disease progression on checkpoint inhibitor and chemotherapy: Preliminary results from the phase 1b/2 OrigAMI-4 study. Oral Oncol. 2025;171:107791. doi:10.1016/j.oraloncology.2025.107791
¹⁰ Haddad R, et al. OrigAMI-5: A randomized, phase 3 study of amivantamab plus pembrolizumab and carboplatin vs standard of care pembrolizumab plus platinum and 5-fluorouracil as first-line treatment in recurrent/metastatic head and neck cancer. Presented at: The 2026 American Society of Clinical Oncology (ASCO) Annual Meeting; May 30, 2026; Chicago, Illinois.
¹¹ RYBREVANT FASPRO™ Prescribing Information. Horsham, PA: Janssen Biotech, Inc.
¹² ClinicalTrials.gov. A Study of Amivantamab Alone or in Addition to Other Treatment Agents in Participants With Recurrent/ Metastatic Head and Neck Cancer (OrigAMI-4). https://clinicaltrials.gov/study/NCT06385080?term=OrigAMI-4&limit=10&rank=1. Accessed May 2026.
¹³ Barsouk A, Aluru JS, Rawla P, Saginala K, Barsouk A. Epidemiology, Risk Factors, and Prevention of Head and Neck Squamous Cell Carcinoma. Med Sci (Basel). 2023;11(2):42. Published 2023 Jun 13. doi:10.3390/medsci11020042
¹⁴ Ghiani L, Chiocca S. High Risk-Human Papillomavirus in HNSCC: Present and Future Challenges for Epigenetic Therapies. International Journal of Molecular Sciences. 2022;23(7):3483. https://doi.org/10.3390/ijms23073483
¹⁵ Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. New England Journal of Medicine. 2016;375(19):1856-1867. doi:10.1056/NEJMoa1602252
¹⁶ Wise-Draper TM, Bahig H, Tonneau M, Karivedu V, Burtness B. Current Therapy for Metastatic Head and Neck Cancer: Evidence, Opportunities, and Challenges. Am Soc Clin Oncol Educ Book. 2022;42:1-14. doi:10.1200/EDBK_350442
¹⁷ Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Non-Small Cell Lung Cancer V.3.2026 © National Comprehensive Cancer Network, Inc. All rights reserved. To view the most recent and complete version of the guideline, go online to NCCN.org. Accessed May 2026.
¹⁸ RYBREVANT^® Prescribing Information. Horsham, PA: Janssen Biotech, Inc.

 

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SOURCE Johnson & Johnson

• Patients were nine times more likely to have little to no cancer remaining in the prostate after surgery, with a 20% reduction in the risk of developing metastasis or death 
• Data selected to open the plenary presentation at ASCO 2026 and published in The New England Journal of Medicine

CHICAGO, May 31, 2026 /PRNewswire/ — Johnson & Johnson (NYSE:JNJ) today announced results from the final analysis of the Phase 3 PROTEUS study showing the investigational use of apalutamide plus hormone therapy (androgen deprivation therapy, ADT), given for six months before and after prostate cancer surgery, significantly improved key short- and long-term clinical outcomes for patients with high-risk localized or locally advanced disease. The trial met both primary endpoints. Patients treated with apalutamide plus hormone therapy were nine times more likely to have little to no cancer remaining at the time of surgery compared with hormone therapy alone (8.9 percent vs. 1.0 percent; pathologic complete response/minimal residual disease). The combination also reduced the risk of developing metastasis or death by 20 percent and extended the time before patients required subsequent therapy to more than six years. These findings will be presented in a plenary session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting (Oral Abstract #LBA1) and published simultaneously in The New England Journal of Medicine.^1,2

The unmet need with standard treatments for patients with high-risk localized prostate cancer

Surgery to remove the prostate (radical prostatectomy) is one of the standard treatments for patients with high-risk localized or locally advanced disease, alongside radiation therapy.^3,4 Yet nearly half of patients who undergo curative-intent surgery will see their cancer return, requiring additional treatment and moving beyond the point where cure is possible.^5,6,7 Additional therapies are often used only after the cancer has spread, missing a critical window to intervene earlier and improve long-term outcomes.⁸ 

Apalutamide blocks androgen hormones from binding to their receptor, which can help slow prostate cancer progression. It is currently approved for use in advanced prostate cancer, including cases where the disease has spread (metastatic castration-sensitive) or is no longer responding to certain hormone therapies (non-metastatic castration-resistant prostate cancer).⁹

Expert perspectives on the perioperative use of ERLEADA^® plus hormone therapy six months before and after prostate cancer surgery

“Reducing the risk of prostate cancer recurrence and death with improved initial treatment regimens has been a longstanding unmet need for patients with localized high-risk prostate cancer,” said Mary-Ellen Taplin,* M.D., FASCO, medical oncologist at Dana-Farber Cancer Institute and Harvard Medical School, and principal investigator. “The PROTEUS trial demonstrates that adding preoperative apalutamide to androgen deprivation therapy and surgery reduced the risk of metastases or death by 20 percent. This result is most impactful as it may reduce the need for subsequent therapies and related side effects, while also increasing potential cure rates. This approach, which combines systemic therapy with surgery, is already standard in other aggressive cancers and now has proven benefit in patients with this disease.”

“For decades, surgery has been the standard approach for many patients with high-risk localized or locally advanced prostate cancer, but these data suggest it may not be enough on its own,” said Adam Kibel,^† M.D., urologic surgeon and chair of the Department of Urology at Mass General Brigham. “Earlier integration of apalutamide has the potential to reshape how prostate cancer is treated by building on curative-intent surgical treatment and improving outcomes for these patients.”

Detailed PROTEUS study results

PROTEUS is a Phase 3 study evaluating apalutamide, an androgen receptor pathway inhibitor, combined with hormone therapy before and after surgery in patients with newly diagnosed high-risk localized or locally advanced prostate cancer (n=2109). The dual primary endpoints were the amount of cancer remaining at surgery (pathologic complete response/minimal residual disease, pCR/MRD) and how long patients lived without the cancer spreading (metastasis-free survival, MFS), both assessed by blinded independent central review.¹

At a median follow-up of 61.7 months, apalutamide plus hormone therapy met both primary endpoints. The rate of pCR/MRD was 8.9 percent with apalutamide plus hormone therapy versus 1.0 percent with hormone therapy alone (odds ratio [OR], 10.17; 95 percent confidence interval [CI], 5.27-19.64; p<0.0001). Apalutamide plus hormone therapy also demonstrated a statistically significant 20 percent reduction in the risk of metastasis or death (hazard ratio [HR], 0.80; 95 percent CI, 0.67-0.96; p=0.02), with five-year rates of 78.2 percent versus 73.5 percent, respectively. Similar metastasis-free survival results were observed in investigator assessments (HR, 0.74; 95 percent CI, 0.62-0.87; p=0.0004).¹

Key secondary endpoints also showed statistically significant and clinically relevant improvement, reinforcing the benefit of the combination across multiple measures of disease control. Notably, patients receiving one year of apalutamide plus hormone therapy before and after surgery went more than six years before needing subsequent therapy, compared to approximately three and a half years with hormone therapy alone (74.2 vs. 41.5 months; HR, 0.65; 95 percent CI, 0.57-0.73; p<0.0001). Most patients also recovered adequate testosterone levels within 8.1 months. Additional benefits included a 29 percent reduction in the risk of disease recurrence or death (event-free survival; HR, 0.71; 95 percent CI, 0.63-0.80; p<0.0001) and improvements in time to distant metastasis (HR, 0.68; 95 percent CI, 0.55-0.83; p=0.0002). Improvements were also seen in MRD as assessed by residual cancer burden rates (30.6 percent vs. 11.7 percent; OR, 3.36; 95 percent CI, 2.67-4.23; nominal p<0.0001), further supporting the depth of response.¹

The safety profile of apalutamide plus hormone therapy was consistent with previous studies. The most common adverse events among patients receiving apalutamide included hot flush (63.4 percent), urinary incontinence (50.2 percent) and erectile dysfunction (41.6 percent). Grade 3 or 4 adverse events occurred in 39.6 percent of patients treated with apalutamide plus hormone therapy, compared to 31.0 percent of those receiving hormone therapy alone. Discontinuations due to adverse events occurred in 7.4 percent and 2.7 percent of patients, respectively. Adverse events of special interest were generally comparable between treatment arms, with a higher incidence of skin rash observed with apalutamide. Rates of deaths were similar between treatment arms. In the apalutamide arm, deaths were more often unrelated to prostate cancer, while in the placebo arm, deaths were more frequently associated with disease progression or metastasis.¹

“These findings point to a new potential way of treating patients with high-risk localized or locally advanced prostate cancer,” said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson. “Apalutamide has already shown an overall survival benefit in advanced disease. Now we’re seeing its impact when used earlier, alongside surgery. As the first therapy in its class to show benefit in this setting, these data reinforce apalutamide’s differentiated profile and the need to move beyond a surgery–only approach to treating earlier and improving long–term outcomes.”

Ongoing study of ERLEADA^® in this setting

Apalutamide plus hormone therapy has not yet been approved by regulatory authorities in this setting. Additional analyses from the PROTEUS study, including ongoing evaluations against current standards of care such as surgery alone, are underway to further contextualize these findings and inform future treatment approaches.

About the PROTEUS study

PROTEUS (NCT03767244) is a randomized, double-blind, placebo-controlled Phase 3 study evaluating apalutamide in combination with androgen deprivation therapy (ADT) in patients with high-risk localized or locally advanced prostate cancer who are candidates for radical prostatectomy. Approximately 2,000 patients were enrolled and randomized to receive apalutamide or placebo, each in combination with ADT, administered before and after radical prostatectomy with pelvic lymph node dissection. Patients with distant metastatic disease, as determined by conventional imaging, were excluded from the study.¹⁰ 

Apalutamide was administered orally at 240 mg once daily. All study participants underwent protocol-defined surgery and were followed for long-term outcomes, including recurrence and progression. The dual primary endpoints of the study are pathologic complete response (pCR) and metastasis-free survival (MFS), with pCR assessed by blinded independent central pathology review and MFS assessed by blinded independent central radiology review.¹⁰

About High-Risk Localized or Locally Advanced Prostate Cancer

Approximately 330,000 people are diagnosed with prostate cancer each year in the U.S.¹¹ Up to 40 percent of patients will be classified as high-risk.¹² Despite advancements in treatment, disease recurrence remains substantial in patients with high-risk localized or locally advanced prostate cancer; up to 50 percent of patients within five years of surgery experience recurrence and carry a significant risk of disease progression and death.^5,6 It’s estimated that more than 36,000 patients will succumb to prostate cancer in 2026, which reinforces the importance of choosing the best possible therapy early for patients with advanced prostate cancer.^8,12

About ERLEADA^®

ERLEADA^® (apalutamide) is an androgen receptor inhibitor indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC). ERLEADA^® received U.S. Food and Drug Administration (FDA) approval for nmCRPC in February 2018 and received U.S. FDA approval for mCSPC in September 2019. To date, more than 340,000 patients worldwide have been treated with ERLEADA^®.⁹ Additional studies are ongoing to evaluate ERLEADA^® in earlier stages of prostate cancer, including high-risk localized and locally advanced disease.

The legal manufacturer for ERLEADA^® is Janssen Biotech, Inc. For more information, visit www.ERLEADAHCP.com.

INDICATIONS

ERLEADA^® (apalutamide) is an androgen receptor inhibitor indicated for the treatment of patients with:

• Metastatic castration-sensitive prostate cancer (mCSPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

ERLEADA^® IMPORTANT SAFETY INFORMATION
⁹

WARNINGS AND PRECAUTIONS

Cerebrovascular and Ischemic Cardiovascular Events, including events leading to death, occurred in patients receiving ERLEADA. Monitor for signs and symptoms of ischemic heart disease and cerebrovascular disorders. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Consider discontinuation of ERLEADA for Grade 3 and 4 events.

In a randomized study (SPARTAN) of patients with nmCRPC, ischemic cardiovascular events occurred in 3.7% of patients treated with ERLEADA and 2% of patients treated with placebo. In a randomized study (TITAN) in patients with mCSPC, ischemic cardiovascular events occurred in 4.4% of patients treated with ERLEADA and 1.5% of patients treated with placebo. Across the SPARTAN and TITAN studies, 4 patients (0.3%) treated with ERLEADA and 2 patients (0.2%) treated with placebo died from an ischemic cardiovascular event. Patients with history of unstable angina, myocardial infarction, congestive heart failure, stroke, or transient ischemic attack within 6 months of randomization were excluded from the SPARTAN and TITAN studies.

In the SPARTAN study, cerebrovascular events occurred in 2.5% of patients treated with ERLEADA and 1% of patients treated with placebo. In the TITAN study, cerebrovascular events occurred in 1.9% of patients treated with ERLEADA and 2.1% of patients treated with placebo. Across the SPARTAN and TITAN studies, 3 patients (0.2%) treated with ERLEADA and 2 patients (0.2%) treated with placebo died from a cerebrovascular event.

Fractures occurred in patients receiving ERLEADA. Evaluate patients for fracture risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents.

In a randomized study (SPARTAN) of patients with nmCRPC, fractures occurred in 12% of patients treated with ERLEADA and in 7% of patients treated with placebo. In a randomized study (TITAN) of patients with mCSPC, fractures occurred in 9% of patients treated with ERLEADA and in 6% of patients treated with placebo.

Falls occurred in patients receiving ERLEADA with increased frequency in the elderly. Evaluate patients for fall risk.

In a randomized study (SPARTAN), falls occurred in 16% of patients treated with ERLEADA compared with 9% of patients treated with placebo. Falls were not associated with loss of consciousness or seizure.

Seizure occurred in patients receiving ERLEADA. Permanently discontinue ERLEADA in patients who develop a seizure during treatment. It is unknown whether anti-epileptic medications will prevent seizures with ERLEADA. Advise patients of the risk of developing a seizure while receiving ERLEADA and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others.

In two randomized studies (SPARTAN and TITAN), five patients (0.4%) treated with ERLEADA and one patient treated with placebo (0.1%) experienced a seizure. Seizure occurred from 159 to 650 days after initiation of ERLEADA. Patients with a history of seizure or, predisposing factors for seizure, or receiving drugs known to decrease the seizure threshold or to induce seizure were excluded. There is no clinical experience in re-administering ERLEADA to patients who experienced a seizure.

Severe Cutaneous Adverse Reactions — Fatal and life-threatening cases of severe cutaneous adverse reactions (SCARs), including Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) occurred in patients receiving ERLEADA.

Monitor patients for the development of SCARs. Advise patients of the signs and symptoms of SCARs (eg, a prodrome of fever, flu-like symptoms, mucosal lesions, progressive skin rash, or lymphadenopathy). If a SCAR is suspected, interrupt ERLEADA until the etiology of the reaction has been determined. Consultation with a dermatologist is recommended. If a SCAR is confirmed, or for other Grade 4 skin reactions, permanently discontinue ERLEADA [see Dosage and Administration (2.2)].

Interstitial Lung Disease (ILD)/Pneumonitis — Fatal and life-threatening interstitial lung disease (ILD) or pneumonitis can occur in patients treated with ERLEADA.

Post-marketing cases of ILD/pneumonitis, including fatal cases, occurred in patients treated with ERLEADA. Across clinical trials (TITAN and SPARTAN, n=1327), 0.8% of patients treated with ERLEADA experienced ILD/pneumonitis, including 0.2% who experienced Grade 3 events [see Adverse Reactions (6.1, 6.2)].

Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever). Immediately withhold ERLEADA if ILD/pneumonitis is suspected.

Permanently discontinue ERLEADA in patients with severe ILD/pneumonitis or if no other potential causes of ILD/pneumonitis are identified [see Dosage and Administration (2.2)].

Embryo-Fetal Toxicity — The safety and efficacy of ERLEADA have not been established in females. Based on findings from animals and its mechanism of action, ERLEADA can cause fetal harm and loss of pregnancy when administered to a pregnant female. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of ERLEADA [see Use in Specific Populations (8.1, 8.3)].

ADVERSE REACTIONS

The most common adverse reactions (≥10%) that occurred more frequently in the ERLEADA-treated patients (≥2% over placebo) from the randomized placebo-controlled clinical trials (TITAN and SPARTAN) were fatigue, arthralgia, rash, decreased appetite, fall, weight decreased, hypertension, hot flush, diarrhea, and fracture.

Laboratory Abnormalities — All Grades (Grade 3-4)

• Hematology — In the TITAN study: white blood cell decreased ERLEADA 27% (0.4%), placebo 19% (0.6%). In the SPARTAN study: anemia ERLEADA 70% (0.4%), placebo 64% (0.5%); leukopenia ERLEADA 47% (0.3%), placebo 29% (0%); lymphopenia ERLEADA 41% (1.8%), placebo 21% (1.6%)
• Chemistry — In the TITAN study: hypertriglyceridemia ERLEADA 17% (2.5%), placebo 12% (2.3%). In the SPARTAN study: hypercholesterolemia ERLEADA 76% (0.1%), placebo 46% (0%); hyperglycemia ERLEADA 70% (2%), placebo 59% (1.0%); hypertriglyceridemia ERLEADA 67% (1.6%), placebo 49% (0.8%); hyperkalemia ERLEADA 32% (1.9%), placebo 22% (0.5%)

Rash — In 2 randomized studies (SPARTAN and TITAN), rash was most commonly described as macular or maculopapular. Adverse reactions of rash were 26% with ERLEADA vs 8% with placebo. Grade 3 rashes (defined as covering >30% body surface area [BSA]) were reported with ERLEADA treatment (6%) vs placebo (0.5%).

The onset of rash occurred at a median of 83 days. Rash resolved in 78% of patients within a median of 78 days from onset of rash. Rash was commonly managed with oral antihistamines and topical corticosteroids, and 19% of patients received systemic corticosteroids. Dose reduction or dose interruption occurred in 14% and 28% of patients, respectively. Of the patients who had dose interruption, 59% experienced recurrence of rash upon reintroduction of ERLEADA.

Hypothyroidism — In 2 randomized studies (SPARTAN and TITAN), hypothyroidism was reported for 8% of patients treated with ERLEADA and 1.5% of patients treated with placebo based on assessments of thyroid-stimulating hormone (TSH) every 4 months. Elevated TSH occurred in 25% of patients treated with ERLEADA and 7% of patients treated with placebo. The median onset was at the first scheduled assessment. There were no Grade 3 or 4 adverse reactions. Thyroid replacement therapy, when clinically indicated, should be initiated or dose adjusted.

DRUG INTERACTIONS

Effect of Other Drugs on ERLEADA

ERLEADA Strong CYP2C8 or CYP3A4 Inhibitors

Reduce the ERLEADA dose as recommended for adverse reactions [see Dosage and Administration (2.2)]. Co-administration of a strong CYP2C8 or CYP3A4 inhibitor is predicted to increase the steady–state exposure of the active moieties (sum of unbound apalutamide plus the potency–adjusted unbound N-desmethyl-apalutamide).

Effect of ERLEADA on Other Drugs

Substrates of CYP3A4, CYP2C9, CYP2C19, P-gp, BCRP, or OATP1B1

Refer to the Prescribing Information for these substrates. Consider alternative agents when possible or evaluate for loss of activity of the substrate if concomitant use cannot be avoided.

• Apalutamide is a strong inducer of CYP3A4 and CYP2C19, a weak inducer of CYP2C9, and an inducer of P-gp, BCRP, and OATP1B1. Apalutamide decreases exposure of substrates of CYP3A4, CYP2C19, CYP2C9, P-gp, BCRP, or OATP1B [see Clinical Pharmacology (12.3)], which may decrease the effectiveness of these substrates.

USE IN SPECIFIC POPULATIONS

The recommended ERLEADA dosage in patients with (Child-Pugh C) is lower than the recommended dosage in patients with normal hepatic function. No dosage modification is recommended for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment.

Please see full 

Prescribing Information
 for ERLEADA.

About Johnson & Johnson

At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.innovativemedicine.jnj.com. Follow us at @JNJInnovMed.

Cautions Concerning Forward-Looking Statements

This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of
ERLEADA^® (apalutamide)
. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s most recent Annual Report on Form 10-K, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com, www.investor.jnj.com or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments.

*Dr. Taplin has provided consulting, advisory, and speaking services to Johnson & Johnson; she has not been paid for any media work.

^†
Dr. Kibel has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work.

__________________________________

¹ Taplin, M. et. al. Perioperative (neoadjuvant and adjuvant) apalutamide (APA) + androgen deprivation therapy (ADT) vs placebo (PBO) + ADT with radical prostatectomy (RP) in high-risk localized or locally advanced prostate cancer (HR LPC/LAPC): Final analysis of the PROTEUS phase 3 study. Presented at: 2026 American Society of Clinical Oncology (ASCO); May 31, 2026; Chicago.

² Taplin ME, Gleave M, Shore ND, et al. Perioperative Apalutamide in High-Risk Localized Prostate Cancer. N Engl J Med. 2026. doi:10.1056/NEJMoa2603878.

³ Young HH. The early diagnosis and radical cure of carcinoma of the prostate. Being a study of 40 cases and presentation of a radical operation which was carried out in four cases. 1905. J Urol. 2002;168:914-21. doi:10.1016/s0022-5347(05)64542-9

⁴ Cooley LF, Shore ND. Historic progression of prostatectomy techniques and associated outcomes. Transl Androl Urol. 2025;14:493-495. doi: 10.21037/tau-2025-3

⁵ Eiber M, et al. PHAROS, a real-world multi-country European study on patients with high-risk localised and locally advanced prostate cancer receiving radical treatment. J Clin Oncol. 2024;42:5024. DOI: 10.1200/JCO.2024.42.16_suppl.502

⁶ Stattin P, et al. Population-based study of disease trajectory after radical treatment for high-risk prostate cancer. BJU Int. 2024;134:96-102. doi.org/10.1111/bju.16362

⁷ National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: prostate cancer. Version 5.2026. Accessed May 2026. https://www.nccn.org.

⁸ American Cancer Society. Initial treatment of prostate cancer, by stage and risk group. Accessed May 2026. https://www.cancer.org/cancer/types/prostate-cancer/treating/by-stage.html 

⁹ ERLEADA^® U.S. Prescribing Information. Horsham, PA: Janssen Biotech, Inc.

¹⁰ ClinicalTrials.gov. A Study of Apalutamide in Participants With High-Risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy (PROTEUS). Available at: https://clinicaltrials.gov/ct2/show/NCT04077463. Accessed May 2026.

¹¹ American Cancer Society. Key statistics for prostate cancer. Accessed May 2026. https://www.cancer.org/cancer/types/prostate-cancer/about/key-statistics.html 

¹² Napodano G, Ferro M, Sanseverino R. High-risk prostate cancer: A very challenging disease in the field of uro-oncology. Diagnostics (Basel). 202126;11(3):400. doi:10.3390/diagnostics11030400

 

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SOURCE Johnson & Johnson

Phase 3 LIBRETTO-432 results establish RET fusions alongside EGFR mutations and ALK fusions as biomarkers in early-stage lung cancer that are associated with dramatic treatment outcomes, underscoring the importance of comprehensive biomarker testing across all stages of disease

These data will be published in the New England Journal of Medicine and simultaneously presented during the Plenary Session at the 2026 ASCO Annual Meeting

INDIANAPOLIS, May 31, 2026 /PRNewswire/ — Eli Lilly and Company (NYSE: LLY) today announced results from the Phase 3 LIBRETTO-432 clinical trial of Retevmo (selpercatinib) as adjuvant therapy versus placebo in patients with early-stage (IB-IIIA) rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC). The study met its primary endpoint, demonstrating a highly statistically significant and clinically meaningful improvement in investigator-assessed event-free survival (EFS) with selpercatinib reducing the risk of disease recurrence or death by 83% versus placebo in the primary analysis population.

These data will be simultaneously published in the New England Journal of Medicineand presented during the Plenary Session at the 2026 ASCO Annual Meeting taking place in Chicago, Illinois, as well as featured in the meeting’s press program.

“Patients with early-stage RET fusion-positive lung cancer face high recurrence risk, yet unlike those with EGFR or ALK alterations, have lacked a proven targeted treatment option,” said Jonathan Goldman, M.D., Professor of Medicine and Director of Clinical Trials at University of California, Los Angeles. “These LIBRETTO-432 results provide strong evidence that treating with selpercatinib after surgery or radiation can significantly lower that risk. The magnitude of benefit seen from adjuvant treatment with selpercatinib reinforces that comprehensive genomic testing at diagnosis is essential for all people with lung cancer and could lead to changes in clinical practice for treating early-stage RET-positive disease.”

LIBRETTO-432 is the first and only randomized Phase 3 study to evaluate the safety and efficacy of a selective RET kinase inhibitor as adjuvant therapy in this population. The trial enrolled 151 patients who were randomized 1:1 to receive selpercatinib 160mg twice daily or placebo for up to three years following completion of definitive radiotherapy or surgery with curative intent with or without adjuvant chemotherapy.

At a median follow-up of 24 months, investigator-assessed EFS in the primary analysis population (patients with stage II-IIIA disease, n=109) was significantly improved with selpercatinib compared to placebo (HR: 0.17 [95% CI, 0.06 to 0.51]; p<0.001). The EFS rate at 24 months was 92% [95% CI, 75.4 to 97.2] for selpercatinib compared to 61% [95% CI, 44.2 to 74.3] for placebo. The median EFS was not reached for selpercatinib versus 31.8 months for placebo. In the overall study population (patients with stage IB-IIIA disease, n=151), EFS was consistent, also favoring selpercatinib (HR: 0.17 [95% CI, 0.06 to 0.49]; p<0.001). The EFS rate at 24 months was 94% [95% CI, 81.5 to 98.0] in the selpercatinib group and 70% [95% CI, 55.5 to 80.1] in the placebo group. Results were consistent across blinded independent central review and key subgroups in both the primary analysis set and in the overall study population. Overall survival results trended in favor of selpercatinib, but were immature at the time of this analysis with few events observed.

The overall safety profile of selpercatinib in LIBRETTO-432 was generally consistent with previously reported trials in the selpercatinib development program. The most common Grade 3 or higher adverse events (AEs) were increased alanine aminotransferase (ALT) (17% in the selpercatinib group versus 1% in the placebo group) and increased aspartate aminotransferase (AST) (19% in the selpercatinib group versus 3% in the placebo group), but were manageable with dose-modification.

“Selpercatinib has changed the treatment paradigm for patients with advanced RET-positive lung cancer, and now the substantial reduction in the risk of recurrence or death seen in LIBRETTO-432 highlights the potential for it to also become a new standard of care in the adjuvant setting for patients with early-stage RET-positive NSCLC,” said Jacob Van Naarden, executive vice president and president of Lilly Oncology. “These compelling results highlight the importance of bringing our effective medicines to patients early in their disease course when their impact can be greatest, and bring further urgency to the need for comprehensive biomarker testing for all lung cancers at diagnosis to enable effective therapy against EGFR, ALK and RET and for the development of medicines targeting emerging new biomarkers.”

Lilly plans to submit results from LIBRETTO-432 to global health authorities. For more information on the LIBRETTO Phase 3 clinical trial program, please visit clinicaltrials.gov.

About LIBRETTO-432
LIBRETTO-432 is a Phase 3, global, multicenter, randomized, double-blind, controlled clinical trial of selpercatinib versus placebo in patients with RET fusion-positive NSCLC following completion of definitive radiotherapy or surgery with curative intent, and other adjuvant therapy, if indicated. The trial enrolled 151 patients who were randomized 1:1 to receive either selpercatinib or placebo as adjuvant therapy for RET fusion-positive NSCLC. The primary endpoint is EFS as assessed by investigator in the primary analysis population, which was comprised of patients with stage II-IIIA RET fusion-positive NSCLC. Secondary endpoints include EFS as assessed by investigator in the overall population, overall survival (OS), EFS as assessed by blinded independent central review (BICR), time to distant disease recurrence in the central nervous system (CNS) as assessed by investigator and BICR, progression-free survival on the next line of treatment (PFS2), positive predictive value (PPV) of RET tests from investigator-identified laboratories with respect to the Lilly-designated RET test, safety and tolerability.

About Retevmo 
Retevmo (selpercatinib, formerly known as LOXO-292) (pronounced reh-TEHV-moh) is a highly selective and potent RET kinase inhibitor with central nervous system (CNS) activity. Retevmo may affect both tumor cells and healthy cells, which can result in side effects. RET-driver alterations are predominantly mutually exclusive from other oncogenic drivers. Retevmo is a U.S. FDA-approved oral prescription medicine, 120 mg or 160 mg dependent on weight (<50 kg or ≥50 kg, respectively), taken twice daily until disease progression or unacceptable toxicity.¹

INDICATIONS FOR RETEVMO (selpercatinib)

RETEVMO is a kinase inhibitor indicated for the treatment of:

• Adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a rearranged during transfection (RET) gene fusion, as detected by an FDA-approved test

IMPORTANT SAFETY INFORMATION FOR RETEVMO (selpercatinib)

Hepatotoxicity: Serious hepatic adverse reactions occurred in 3% of patients treated with Retevmo. Increased aspartate aminotransferase (AST) occurred in 59% of patients, including Grade 3 or 4 events in 11% and increased alanine aminotransferase (ALT) occurred in 55% of patients, including Grade 3 or 4 events in 12%. Monitor ALT and AST prior to initiating Retevmo, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose, or permanently discontinue Retevmo based on severity.

Severe, life-threatening, and fatal interstitial lung disease (ILD)/pneumonitis can occur in patients treated with Retevmo. ILD/pneumonitis occurred in 1.8% of patients who received Retevmo, including 0.3% with Grade 3 or 4 events, and 0.3% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold Retevmo and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Withhold, reduce dose, or permanently discontinue Retevmo based on severity of confirmed ILD.

Hypertension occurred in 41% of patients, including Grade 3 hypertension in 20% and Grade 4 in one (0.1%) patient. Overall, 6.3% had their dose interrupted and 1.3% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate Retevmo in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Retevmo. Monitor blood pressure after 1 week, at least monthly thereafter, and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue Retevmo based on severity.

Retevmo can cause concentration-dependent QT interval prolongation. An increase in QTcF interval to >500 ms was measured in 7% of patients and an increase in the QTcF interval of at least 60 ms over baseline was measured in 20% of patients. Retevmo has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction. Monitor patients who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure. Assess QT interval, electrolytes, and thyroid-stimulating hormone (TSH) at baseline and periodically during treatment, adjusting frequency based upon risk factors including diarrhea. Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating Retevmo and during treatment. Monitor the QT interval more frequently when Retevmo is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and dose reduce or permanently discontinue Retevmo based on the severity.

Serious, including fatal, hemorrhagic events can occur with Retevmo. Grade ≥3 hemorrhagic events occurred in 3.1% of patients treated with Retevmo including 4 (0.5%) patients with fatal hemorrhagic events, including cerebral hemorrhage (n=2), tracheostomy site hemorrhage (n=1), and hemoptysis (n=1). Permanently discontinue Retevmo in patients with severe or life-threatening hemorrhage.

Retevmo can cause hypersensitivity, including severe skin reactions such as Stevens-Johnson Syndrome. All grade hypersensitivity occurred in 6% of patients receiving Retevmo, including Grade 3 in 1.9%. The median time to onset was 1.9 weeks (range: 5 days to 2 years). Signs and symptoms of hypersensitivity included fever, rash and arthralgias or myalgias with concurrent decreased platelets or transaminitis. Stevens-Johnson Syndrome has been observed in the post-marketing setting. Discontinue Retevmo in patients with Stevens-Johnson Syndrome. If hypersensitivity occurs, withhold Retevmo and begin corticosteroids at a dose of 1 mg/kg prednisone (or equivalent). Upon resolution of the event, resume Retevmo at a reduced dose and increase the dose of Retevmo by 1 dose level each week as tolerated until reaching the dose taken prior to onset of hypersensitivity. Continue steroids until patient reaches target dose and then taper. Permanently discontinue Retevmo for recurrent hypersensitivity.

Tumor lysis syndrome (TLS) occurred in 0.6% of patients with medullary thyroid carcinoma receiving Retevmo. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated.

Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, Retevmo has the potential to adversely affect wound healing. Withhold Retevmo for at least 7 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Retevmo after resolution of wound healing complications has not been established.

Retevmo can cause hypothyroidism. Hypothyroidism occurred in 13% of patients treated with Retevmo; all reactions were Grade 1 or 2. Hypothyroidism occurred in 13% of patients (50/373) with thyroid cancer and 13% of patients (53/423) with other solid tumors including NSCLC. Monitor thyroid function before treatment with Retevmo and periodically during treatment. Treat with thyroid hormone replacement as clinically indicated. Withhold Retevmo until clinically stable or permanently discontinue Retevmo based on severity.

Based on data from animal reproduction studies and its mechanism of action, Retevmo can cause fetal harm when administered to a pregnant woman. Administration of selpercatinib to pregnant rats during organogenesis at maternal exposures that were approximately equal to those observed at the recommended human dose of 160 mg twice daily resulted in embryolethality and malformations. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Retevmo and for 1 week after the last dose. There are no data on the presence of selpercatinib or its metabolites in human milk or on their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Retevmo and for 1 week after the last dose.

Severe adverse reactions (Grade 3-4) occurring in
≥
20% of patients who received Retevmo in LIBRETTO-001, were hypertension (20%), diarrhea (5%), prolonged QT interval (4.8%), dyspnea (3.1%), fatigue (3.1%), hemorrhage (2.6%), abdominal pain (2.5%), vomiting (1.8%), headache (1.4%), nausea (1.1%), constipation (0.8%), edema (0.8%), rash (0.6%), and arthralgia (0.3%).

Severe adverse reactions (Grade 3-4) occurring in
≥
15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431 were hypertension (20% vs 3.1%), electrocardiogram QT prolonged (9% vs 0%), fatigue (3.2% vs 5%), edema (2.5% vs 0%), rash (1.9% vs 1.0%), diarrhea (1.3% vs 2.0%), abdominal pain (0.6% vs 2.0%), pyrexia (0.6% vs 0%), COVID19 infection (0.6% vs 0%), constipation (0% vs 1.0%), nausea (0% vs 1.0%), vomiting (0% vs 1.0%), and decreased appetite (0% vs 2.0%).

Serious adverse reactions
occurred in 44% of patients
who received Retevmo
in LIBRETTO-001. The most frequently reported serious adverse reactions (in ≥2% of patients) were pneumonia, pleural effusion, abdominal pain, hemorrhage, hypersensitivity, dyspnea, and hyponatremia. Fatal adverse reactions occurred in 3% of patients in LIBRETTO-001; fatal adverse reactions included sepsis (n=6), respiratory failure (n=5), hemorrhage (n=4), pneumonia (n=3), pneumonitis (n=2), cardiac arrest (n=2), sudden death (n=1), and cardiac failure (n=1).

Serious adverse reactions occurred in 35% of patients who received Retevmo in LIBRETTO-431. The most frequently reported serious adverse reactions (≥2% of patients) were pleural effusion and abnormal hepatic function. Fatal adverse reactions occurred in 4.4% of patients who received Retevmo in LIBRETTO-431; fatal adverse reactions included myocardial infarction (n=2), respiratory failure (n=2), cardiac arrest, malnutrition, and sudden death (n=1 each).

Common adverse reactions (all grades) occurring in
≥
20% of patients who received Retevmo in LIBRETTO-001, were edema (49%), diarrhea (47%), fatigue (46%), dry mouth (43%), hypertension (41%), abdominal pain (34%), rash (33%), constipation (33%), nausea (31%), headache (28%), cough (24%), vomiting (22%), dyspnea (22%), hemorrhage (22%), arthralgia (21%), and prolonged QT interval (21%).

Common adverse reactions (all grades) occurring in
≥
15% of patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431 were hypertension (48% vs 7%), diarrhea (44% vs 24%), edema (41% vs 28%), dry mouth (39% vs 6%), rash (33% vs 30%), fatigue (32% vs 50%), abdominal pain (25% vs 19%), musculoskeletal pain (25% vs 28%), constipation (22% vs 40%), electrocardiogram QT prolonged (20% vs 1.0%), COVID19 infection (19% vs 18%), stomatitis (18% vs 16%), decreased appetite (17% vs 34%), nausea (13% vs 44%), vomiting (13% vs 23%), and pyrexia (13% vs 23%).

Laboratory abnormalities (all grades
≥
20%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-001, were increased AST (59%; 11%), decreased calcium (59%; 5.7%), increased ALT (56%; 12%), decreased albumin (56%; 2.3%), increased glucose (53%; 2.8%), decreased lymphocytes (52%; 20%), increased creatinine (47%; 2.4%), decreased sodium (42%; 11%), increased alkaline phosphatase (40%; 3.4%), decreased platelets (37%; 3.2%), increased total cholesterol (35%; 1.7%), increased potassium (34%; 2.7%), decreased glucose (34%; 1.0%), decreased magnesium (33%; 0.6%), increased bilirubin (30%; 2.8%), decreased hemoglobin (28%; 3.5%), and decreased neutrophils (25%; 3.2%).

Laboratory abnormalities (all grades
≥
20%; Grade 3-4) worsening from baseline in patients who received Retevmo or chemotherapy with or without pembrolizumab in LIBRETTO-431 were increased ALT (81%; 21% vs 63%; 4.1%), increased AST (77%; 10% vs 46%; 0%), decreased calcium (53%; 1.9% vs 24%; 1.0%), decreased platelets (53%; 3.2% vs 39%; 5%), decreased lymphocytes (53%; 8% vs 64%; 15%), decreased neutrophils (53%; 2.0% vs 58%; 11%), increased bilirubin (52%; 1.3% vs 9%; 0%), increased alkaline phosphatase (35%; 1.3% vs 22%; 0%), decreased sodium (31%; 3.2% vs 41%; 2.1%), decreased albumin (25%; 0% vs 5%; 0%), increased blood creatinine (23%; 0% vs 21%; 0%), decreased hemoglobin (21%; 0% vs 91%; 5%), decreased potassium (17%; 1.3% vs 15%; 1.0%), and decreased magnesium (16%; 0.6% vs 8%; 0%).

Concomitant use of acid-reducing agents decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid concomitant use of proton-pump inhibitors (PPIs), histamine-2 (H2) receptor antagonists, and locally acting antacids with Retevmo. If coadministration cannot be avoided, take Retevmo with food (with a PPI) or modify its administration time (with a H2 receptor antagonist or a locally acting antacid).

Concomitant use of strong and moderate CYP3A inhibitors increases selpercatinib plasma concentrations which may increase the risk of Retevmo adverse reactions including QTc interval prolongation. Avoid concomitant use of strong and moderate CYP3A inhibitors with Retevmo. If concomitant use of a strong or moderate CYP3A inhibitor cannot be avoided, reduce the Retevmo dosage as recommended and monitor the QT interval with ECGs more frequently.

Concomitant use of strong and moderate CYP3A inducers decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid coadministration of Retevmo with strong and moderate CYP3A inducers.

Concomitant use of Retevmo with CYP2C8 and CYP3A substrates increases their plasma concentrations which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with CYP2C8 and CYP3A substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for CYP2C8 and CYP3A substrates provided in their approved product labeling.

Retevmo is a P-glycoprotein (P-gp) and BCRP inhibitor. Concomitant use of Retevmo with P-gp or BCRP substrates increases their plasma concentrations, which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with P-gp or BCRP substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for P-gp and BCRP substrates provided in their approved product labeling.

No dosage modification is recommended for patients with mild to severe renal impairment (estimated Glomerular Filtration Rate [eGFR] ≥15 to 89 mL/min, estimated by Modification of Diet in Renal Disease [MDRD] equation). A recommended dosage has not been established for patients with end-stage renal disease.

Reduce the dose when administering Retevmo to patients with severe hepatic impairment (total bilirubin greater than 3 to 10 times upper limit of normal [ULN] and any AST). No dosage modification is recommended for patients with mild or moderate hepatic impairment. Monitor for Retevmo-related adverse reactions in patients with hepatic impairment.

Retevmo (selpercatinib) is available as 40 mg and 80 mg capsules, and 40 mg, 80 mg, 120 mg, and 160 mg tablets.

SE HCP ISI LA_NOV2025

Please see full

Prescribing Information, including Instructions for Use

, for Retevmo.

About Lilly           
Lilly is a medicine company turning science into healing to make life better for people around the world. We’ve been pioneering life-changing discoveries for 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world’s most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer’s disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we’re motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram, and LinkedIn. P-LLY

© Lilly USA, LLC 2026. ALL RIGHTS RESERVED. 

Trademarks and Trade Names
All trademarks or trade names referred to in this press release are the property of the company, or, to the extent trademarks or trade names belonging to other companies are references in this press release, the property of their respective owners. Solely for convenience, the trademarks and trade names in this press release are referred to without the ® and ™ symbols, but such references should not be construed as any indicator that the company or, to the extent applicable, their respective owners will not assert, to the fullest extent under applicable law, the company’s or their rights thereto. We do not intend the use or display of other companies’ trademarks and trade names to imply a relationship with, or endorsement or sponsorship of us by, any other companies.

Cautionary Statement Regarding Forward-Looking Statements 
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Retevmo as a potential treatment for rearranged during transfection (RET) fusion-positive stage IB-IIIA NSCLC following completion of definitive radiotherapy or surgery with curative intent, and other adjuvant therapy if indicated, and reflects Lilly’s current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with study results to date, or that Retevmo will receive additional regulatory approvals. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly’s expectations, see Lilly’s Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release. 
 
Endnotes & References 

1. Retevmo. Prescribing information. Lilly USA, LLC.

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SOURCE Eli Lilly and Company