Oric Pharmaceuticals (NASDAQ:ORIC) reported updated Phase 1b data for enozertinib in previously untreated patients with advanced non-small cell lung cancer (NSCLC) carrying atypical EGFR mutations, highlighting systemic and intracranial responses in a cohort with a high prevalence of baseline brain metastases.
The company said the results, presented at the European Society for Medical Oncology meeting, were based on a Sept. 4, 2026 data cutoff and included 26 patients treated with enozertinib monotherapy at a recommended Phase 3 dose of 80 milligrams once daily. Patients had PACC mutations or L861X mutations, including L861Q.
Response Data and CNS Activity
Among 25 response-evaluable patients, enozertinib produced an 88% best overall response rate and an 84% confirmed overall response rate by investigator assessment, according to Chief Medical Officer Pratik Multani. The confirmed response rate by blinded independent central review was 80%.
All four patients who did not achieve a confirmed partial response had stable disease, resulting in a 100% disease-control rate in the response-evaluable population, the company said. In circulating tumor DNA assessments, all 22 evaluable patients had at least a 90% reduction in EGFR-mutant ctDNA, while 82% achieved full clearance within the first two treatment cycles.
The trial population included a substantial proportion of patients with central nervous system involvement. Seventeen of 26 patients, or 65%, had brain metastases at baseline, including 12 patients with previously untreated brain metastases.
In the 10 patients with measurable CNS lesions assessed by investigators, the confirmed intracranial response rate was 70%, including two complete responses. The remaining three patients had stable disease with tumor shrinkage. Under blinded independent central review using RANO-BM criteria, 15 patients were evaluable for CNS response; the confirmed intracranial response rate was 67%, including six complete responses.
Multani said no new CNS lesions emerged in patients during the reported analysis, regardless of whether brain metastases were present at baseline. At a median follow-up of 10.5 months, median progression-free survival and median duration of response had not been reached. The six-month landmark progression-free survival estimate was 88%.
Safety Profile
Oric said treatment-related adverse events were primarily Grade 1 or Grade 2. Grade 3 treatment-related events occurred in six patients, or 23%, and resolved with dose modifications. The company reported no Grade 4 or Grade 5 treatment-related events and no treatment-related discontinuations.
The most common treatment-related adverse events were diarrhea, paronychia, rash, acneiform dermatitis and stomatitis. Multani said the safety findings were consistent with EGFR wild-type inhibition and that the study did not show significant cardiac, hematologic or hepatic off-target toxicities.
Chief Executive Officer Jacob Chacko said the company believes the combined systemic activity, CNS activity and tolerability could support a potential best-in-class profile in the first-line atypical EGFR NSCLC setting. However, the Phase 1b dataset remains small and follow-up for progression-free survival is ongoing.
Phase 3 Plans
Oric said it has completed end-of-Phase-1 discussions with the Food and Drug Administration and plans to begin REDWOOD-1, a global randomized Phase 3 trial, in the first half of 2027.
The study is expected to enroll treatment-naive patients with advanced NSCLC harboring PACC or L861X atypical EGFR mutations. Participants will be randomized one-to-one to enozertinib at 80 milligrams daily or physician’s choice of osimertinib or afatinib. Patients with treated and stable brain metastases, as well as untreated but asymptomatic brain metastases, will be eligible.
The trial will use dual primary endpoints: blinded independent central review of overall response rate, intended to support a potential accelerated approval, and blinded independent central review of progression-free survival, intended as a confirmatory endpoint for full approval. Overall survival and intracranial response rate are planned as key secondary endpoints.
Multani said the company expects to conduct further regulatory discussions outside the U.S. before activating the global study. The company has not provided timing expectations for top-line Phase 3 data.
Commercial and Exon 20 Development
Oric estimates that first-line atypical EGFR NSCLC represents an annual U.S. market opportunity of more than $2.5 billion and a global opportunity above $5 billion. The company based those estimates on an approximately 7,000-patient annual U.S. incidence estimate, an assumed 15-month treatment duration and current EGFR tyrosine kinase inhibitor pricing.
The company also continues to study enozertinib in EGFR exon 20 insertion NSCLC. Chacko said Oric is evaluating monotherapy, chemotherapy combination and amivantamab combination approaches in that setting and expects to share data from all three cohorts concurrently in mid-2027. Following those results, the company could potentially initiate a separate REDWOOD-2 study.
Oric said its previously stated cash runway into the second half of 2028 already incorporates the planned REDWOOD-1 study as well as its ongoing Phase 3 program for rinzimetostat.
About Oric Pharmaceuticals (NASDAQ:ORIC)
Oric Pharmaceuticals, Inc (NASDAQ: ORIC) is a clinical-stage biopharmaceutical company focused on developing medicines that overcome mechanisms of treatment resistance in cancer. The company uses its discovery platform to identify therapies intended to improve or restore the effectiveness of existing cancer treatments.
Oric’s pipeline has included ORIC-533, an oral small-molecule inhibitor of CD73 designed to block adenosine-mediated immunosuppression in the tumor microenvironment. The company has evaluated the program in hematologic malignancies, including multiple myeloma.
