Oric Pharmaceuticals presents data from enozertinib trial at ESMO Asia

Oric Pharmaceuticals (ORIC) announced data from a Phase 1b trial of enozertinib at the ESMO Asia Congress 2025. Data in previously treated NSCLC patients with EGFR atypical mutations were presented at a mini-oral session. In addition, compelling preliminary data in 1L NSCLC patients with EGFR P-loop and alpha C-helix compressing mutations were disclosed. As of the August 29 cutoff date, 47 patients were dosed, 25 patients received 80 mg QD oral enozertinib and 22 patients received 120 mg QD. Patients were heavily pretreated, having received a median of two 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. Enozertinib was well tolerated with mostly Grade 1 or 2 treatment-related adverse events 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. Overall, 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. In the 22 efficacy evaluable patients with PACC mutations, enozertinib demonstrated systemic and CNS antitumor activity. In total, 36% confirmed ORR and 91% DCR, with comparable rates in patients with brain metastases at baseline. Responses observed across a wide range of EGFR PACC mutations including in the most prevalent mutations and in a broad spectrum of PACC complex mutations. As of the data cutoff, 75% of responders remained on treatment. As of the November 18 cutoff date, 10 efficacy evaluable patients were dosed with 80 mg QD oral enozertinib. 60% of these patients had brain metastases at baseline, all of which were active and untreated. The safety profile to date in this cohort of patients is in line with the safety profile at the 80 mg QD dose level in other cohorts. Enozertinib demonstrated preliminary systemic and CNS activity, including 80% ORR and 100% intracranial ORR in patients with measurable CNS disease. Based on these data, 80 mg QD oral enozertinib has been selected as the dose for potential Phase 3 development. Enrollment and follow-up continues in 1L EGFR PACC patients with the next update expected in mid-2026, ahead of initiation of a potential Phase 3 trial.