Oric Pharmaceuticals (ORIC) Study update summary

Study population and design

• Phase Ib study across 39 academic centers in 10 countries; at the Sep. 4, 2026 cutoff, 26 treatment-naive patients received enozertinib 80 mg once daily: 23 with PACC mutations and 3 with L861Q without co-occurring PACC mutations.

• Baseline brain metastases were present in 65% of patients; 12/26 (46%) had untreated brain metastases at enrollment.

Efficacy results

• Confirmed systemic ORR was 84% (21/25) by investigator assessment and 80% (20/25) by BICR; investigator-assessed best ORR was 88% and disease control rate was 100%.

• Investigator-assessed confirmed intracranial ORR was 70%, including 2 complete responses among 10 patients with measurable CNS lesions; BICR RANO-BM ORR was 67% (10/15), with 6 complete responses (40%).

• Five of six BICR CNS complete responses occurred in patients with untreated brain metastases; no new CNS lesions were observed during the update.

• All 22 evaluable patients achieved at least 90% EGFR-mutant ctDNA reduction, and 82% achieved full clearance within the first 2 treatment cycles; all response-evaluable patients reached MR90 by Cycle 3 Day 1.

• At median follow-up of 10.5 months, 6-month landmark PFS was 88%; median time on treatment was not reached, and median PFS and duration of response remained immature.

Safety

• Treatment-related adverse events were predominantly Grade 1–2; Grade 3 events occurred in 6 patients (23%) and resolved with dose modification, with no Grade 4/5 events or treatment-related discontinuations.

• Common events included diarrhea, paronychia, rash, acneiform dermatitis and stomatitis; no significant off-target cardiac, hematologic or hepatic toxicity was reported.