{"id":916691,"date":"2025-12-04T21:49:31","date_gmt":"2025-12-05T02:49:31","guid":{"rendered":"https:\/\/www.marketnewsdesk.com\/index.php\/oric-pharmaceuticals-presents-potential-best-in-class-profile-for-enozertinib-with-robust-systemic-and-cns-activity-in-1l-and-previously-treated-nsclc-patients-with-egfr-atypical-mutations-at-th\/"},"modified":"2025-12-04T21:49:31","modified_gmt":"2025-12-05T02:49:31","slug":"oric-pharmaceuticals-presents-potential-best-in-class-profile-for-enozertinib-with-robust-systemic-and-cns-activity-in-1l-and-previously-treated-nsclc-patients-with-egfr-atypical-mutations-at-th","status":"publish","type":"post","link":"https:\/\/www.marketnewsdesk.com\/index.php\/oric-pharmaceuticals-presents-potential-best-in-class-profile-for-enozertinib-with-robust-systemic-and-cns-activity-in-1l-and-previously-treated-nsclc-patients-with-egfr-atypical-mutations-at-th\/","title":{"rendered":"ORIC\u00ae Pharmaceuticals Presents Potential Best-in-Class Profile for Enozertinib with Robust Systemic and CNS Activity in 1L and Previously Treated NSCLC Patients with EGFR Atypical Mutations at the ESMO Asia Congress 2025"},"content":{"rendered":"
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\n Highly differentiated 1L EGFR PACC preliminary systemic activity of 80% ORR and 100% intracranial ORR, including in patients with active brain metastases<\/em>\n <\/p>\n

\n 36% ORR in median 3L EGFR PACC patients exceeds competitor benchmarks<\/em>\n <\/p>\n

\n Competitive safety profile, with no significant off-target toxicity and manageable on-target toxicity, resulting in low discontinuation rate<\/em>\n <\/p>\n

\n Enrollment and follow-up continue in 1L EGFR PACC patients at selected dose of 80 mg once daily, with next update expected mid-2026 ahead of initiation of potential Phase 3 trial<\/em>\n <\/p>\n

\n Company to host a conference call and webcast on Saturday, December 6, 2025, at 8:00 pm ET<\/em>\n <\/p>\n

SOUTH SAN FRANCISCO and SAN DIEGO, Dec. 04, 2025 (GLOBE NEWSWIRE) — ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, announced data from a Phase 1b trial of enozertinib (ORIC-114) at the ESMO Asia Congress 2025. Data in previously treated NSCLC patients with EGFR atypical mutations were presented at a mini-oral session, and the presentation can be found in the publication section of ORIC\u2019s website here<\/a>. In addition, compelling preliminary data in 1L NSCLC patients with EGFR P-loop and alpha C-helix compressing (PACC) mutations were disclosed.<\/p>\n

\u201cEnozertinib was purposefully designed to be highly brain-penetrant and exquisitely selective in order to address the limitations of available therapies and potentially drive differentiated durability. These data provide clinical support for this design approach, demonstrating strong systemic and CNS activity in NSCLC patients with EGFR PACC mutations,\u201d said Pratik S. Multani, M.D., chief medical officer. \u201cThe profile we have seen with enozertinib compares favorably to other investigational therapies and continues to support enozertinib\u2019s best-in-class potential.\u201d<\/p>\n

\n Enozertinib Phase 1b Trial Design<\/strong>
\n
Enozertinib is being evaluated in a Phase 1b trial in patients with locally advanced or metastatic NSCLC with EGFR atypical mutations. Notably, enrollment allows patients with active untreated brain metastases. Prior therapies in previously treated patients include chemotherapy and EGFR targeted therapies. The primary endpoint of the trial is to determine the recommended Phase 2 dose (RP2D), and secondary endpoints include investigator-assessed objective response rate (ORR), disease control rate (DCR), and safety.<\/p>\n

\n Previously Treated NSCLC Patients with EGFR Atypical Mutations<\/strong>
\n
As of the August 29, 2025 cutoff date, 47 patients were dosed \u2014 25 patients received 80 mg QD oral enozertinib and 22 patients received 120 mg QD. Patients were heavily pretreated, having received a median of 2 prior therapies, with 81% of patients having received a prior EGFR targeted therapy, including osimertinib and afatinib. Brain metastases were present in 55% of patients at baseline, including those with active brain metastases.<\/p>\n

\n Preliminary Safety Analysis<\/u>
\n
Enozertinib was well tolerated with mostly Grade 1 or 2 treatment-related adverse events (TRAEs) and no significant off-target toxicities. Most frequent TRAEs included diarrhea, paronychia, and stomatitis. There were no treatment discontinuations related to TRAEs. High rates of early dose reductions occurred in the 120 mg cohort compared to the 80 mg cohort, such that most patients received an effective dose of 80 mg QD.<\/p>\n

22 patients with PACC mutations were efficacy evaluable, all receiving an effective dose of 80 mg QD, consisting of 12 patients from the 80 mg cohort and 10 patients from the 120 mg cohort who underwent early dose reduction.<\/p>\n

\n Preliminary Activity Analysis<\/u>
\n
In the 22 efficacy evaluable patients with PACC mutations, enozertinib demonstrated strong systemic and CNS antitumor activity.<\/p>\n