ORIC Pharmaceuticals, Inc. reported updated clinical data for its drug candidate enozertinib (ORIC-114) during an October 23, 2026 presentation at the ESMO Congress 2026. The company presented data from a Phase 1b trial evaluating enozertinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) carrying epidermal growth factor receptor (EGFR) atypical and exon 20 insertion mutations.
As of a September 4, 2026 cutoff date, data were presented for 26 patients treated with 80 mg of enozertinib once daily. Of these patients, 23 had P-loop and αC-helix compressing (PACC) mutations, and 3 had L861Q mutations. Notably, 65% of the patient population had brain metastases at baseline, with 46% having untreated lesions. The trial assessed safety, recommended Phase 2 dose, and antitumor activity.
Regarding safety, enozertinib was described as well tolerated. Treatment-related adverse events were predominantly Grade 1 or 2. The most frequent events included diarrhea, paronychia, and dermatitis acneiform. Six patients (23%) experienced Grade 3 treatment-related adverse events, all of which were resolved with dose modifications. No Grade 4 or 5 events or treatment discontinuations due to adverse events were reported.
The data indicated meaningful systemic antitumor activity. For 25 response-evaluable patients, the confirmed objective response rate (ORR) by investigator assessment was 84% (21 of 25), while the blinded independent central review (BICR) ORR was 80% (20 of 25). Additionally, 100% of patients achieved MR90, defined as a reduction of at least 90% in EGFR-mutant circulating tumor DNA (ctDNA), and 82% achieved full clearance of the mutation.
Enozertinib also demonstrated compelling intracranial activity. All response-evaluable patients with measurable CNS disease achieved tumor reductions. The confirmed intracranial ORR by investigator assessment was 70%. When assessed using the more stringent BICR RANO-BM criteria, the intracranial ORR was 67% (10 of 15), and the intracranial complete response rate was 40% (6 of 15).
Based on these results and interactions with the U.S. Food and Drug Administration, ORIC plans to initiate the Redwood-1 trial in the first half of 2027. This global Phase 3 registrational trial will enroll approximately 360 patients with PACC and L861X mutations, including those with untreated brain metastases. Patients will be randomized to receive 80 mg of enozertinib daily or a physician's choice of osimertinib or afatinib. The trial will evaluate objective response rate by BICR and progression-free survival by BICR as dual primary endpoints.
