SOUTH SAN FRANCISCO and SAN DIEGO, Calif. — October 23, 2026
ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical-stage oncology company developing treatments to overcome therapeutic resistance, presented new clinical data for enozertinib (ORIC-114) in previously untreated patients with non-small cell lung cancer (NSCLC) harboring EGFR atypical mutations at the ESMO Congress 2026. Based on the findings, the company plans to advance enozertinib into Redwood-1, a global Phase 3 registrational trial, with initiation expected in the first half of 2027. In the ongoing Phase 1b study, enozertinib demonstrated a confirmed systemic objective response rate (ORR) of 84% by investigator assessment and a confirmed intracranial ORR of 70% in the first-line EGFR atypical NSCLC population. The results are notable because 65% of patients had brain metastases at baseline, including 46% with previously untreated brain metastases. ORIC said this proportion was more than twice the rate in comparator datasets. The company characterized the findings as potentially best-in-class, while noting that follow-up remains ongoing and longer-term progression-free survival (PFS) and duration-of-response data are immature. Enozertinib remains investigational and has not been established as a standard treatment through a completed Phase 3 trial.
Phase 1b Trial Demonstrates Broad Antitumor Activity
As of the September 4, 2026 data cutoff, the reported analysis included 26 patients receiving oral enozertinib at 80 mg once daily. The population comprised 23 patients with P-loop and alpha C-helix compressing (PACC) mutations and three patients with L861Q mutations without a co-occurring PACC mutation. The ongoing Phase 1b trial evaluates patients with locally advanced or metastatic NSCLC carrying EGFR atypical or EGFR exon 20 insertion mutations, and permits enrollment of patients with active, untreated brain metastases. Confirmed systemic ORR was 84% (21 of 25 patients) by investigator assessment and 80% (20 of 25) by blinded independent central review (BICR). Tumor reductions were observed across response-evaluable patients and a range of mutations, including G719X, S768I, complex PACC mutations and L861Q mutations. Molecular response findings also indicated substantial reductions in circulating tumor DNA. Among 22 patients with baseline plasma EGFR mutations and an opportunity for two post-baseline systemic tumor assessments, 100% achieved MR90, defined as a reduction of at least 90% in EGFR-mutant circulating tumor DNA, while 82% achieved full clearance by Cycle 3 Day 1. These molecular findings are exploratory and do not independently establish a long-term survival benefit for enozertinib.
Intracranial Responses and Early Durability Findings
Enozertinib also demonstrated intracranial activity in patients with baseline central nervous system (CNS) metastases. Among patients with measurable target CNS lesions assessed by investigators, the reported confirmed intracranial ORR was 70%. Under the more stringent BICR assessment using Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria, the intracranial ORR was 67% (10 of 15 patients). The BICR analysis also reported an intracranial complete response rate of 40% (6 of 15 patients), including three patients with non-measurable CNS disease. ORIC reported that no new CNS lesions were observed in patients with or without baseline CNS metastases during the reported analysis. The study’s Kaplan-Meier estimate for six-month landmark PFS was 88%. However, median PFS and median duration of response had not yet matured, and most patients remained on treatment at the data cutoff. These early findings require further evaluation in larger, controlled studies before the magnitude and durability of clinical benefit can be established. ORIC Chief Medical Officer Pratik S. Multani, M.D., highlighted the proportion of participants with baseline brain metastases when discussing the systemic and intracranial responses. The company said the findings, alongside completed End-of-Phase 1 interactions with the U.S. Food and Drug Administration (FDA), support progression into a registrational study.
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Redwood-1 Phase 3 Trial Planned for 2027
ORIC plans to initiate Redwood-1 in the first half of 2027. The proposed global Phase 3 trial is expected to enroll approximately 360 patients with first-line EGFR atypical NSCLC carrying PACC or L861X mutations, including patients with untreated brain metastases. Participants are planned to be randomized to receive enozertinib 80 mg orally once daily or physician’s choice of osimertinib or afatinib. The planned dual primary endpoints are ORR assessed by BICR, intended to support a potential accelerated approval pathway, and PFS assessed by BICR, intended to support full approval. Key secondary endpoints include overall survival and intracranial ORR assessed by BICR using RANO-BM criteria. These are planned trial objectives, not established regulatory outcomes. ORIC President and Chief Executive Officer Jacob M. Chacko said the program is part of the company’s effort to expand its clinical-stage oncology portfolio, which also includes rinzimetostat, a PRC2 inhibitor being developed for prostate cancer. The ESMO data were presented in a poster titled “Enozertinib (ORIC-114), a Brain Penetrant, Highly Selective EGFR Inhibitor, in Treatment-Naive Metastatic NSCLC with EGFR Atypical Mutations.” The presentation was scheduled for October 26, 2026, during the metastatic NSCLC session. ORIC also announced a conference call and webcast featuring Joshua Sabari, M.D., of NYU Grossman School of Medicine, to discuss the findings and their potential implications.
Source: ORIC Pharmaceuticals, press release
