ORIC® Pharmaceuticals Presents Potential Best-in-Class Profile for Enozertinib with Robust Systemic and CNS Activity in 1L and 2L NSCLC Patients with EGFR Exon 20 Mutations at the ESMO Asia Congress 2025

Core Insights - ORIC Pharmaceuticals announced promising data from a Phase 1b trial of enozertinib (ORIC-114) for treating NSCLC patients with EGFR exon 20 mutations, showing a 67% overall response rate (ORR) and 100% intracranial ORR in treatment-naïve patients with active brain metastases [1][2][16] - The drug demonstrated a 45% ORR in previously treated (2L) patients, surpassing competitor benchmarks, and exhibited a competitive safety profile with manageable on-target toxicity [1][4][5] - The company plans to continue enrollment and follow-up in 1L patients at a selected dose of 80 mg once daily, with the next update expected in mid-2026 ahead of a potential Phase 3 trial [1][12] Trial Design and Patient Demographics - The Phase 1b trial is evaluating enozertinib in patients with locally advanced or metastatic NSCLC with EGFR exon 20 mutations, allowing enrollment of patients with active untreated brain metastases [3] - As of August 29, 2025, 45 2L patients were dosed, with 38% having brain metastases at baseline [4] - In the 1L cohort, 33 patients were dosed, with 39% presenting with brain metastases [7] Safety and Efficacy Analysis - Preliminary safety analysis indicated that enozertinib was well tolerated, with most treatment-related adverse events (TRAEs) being Grade 1 or 2, and only a small number of patients discontinuing treatment due to TRAEs [5][9] - In the 80 mg cohort, 67% of responders remained on treatment at a median follow-up of over 30 weeks, while in the 120 mg cohort, 80% of patients underwent early dose reductions due to TRAEs [8][10][16] - The drug showed strong systemic and CNS antitumor activity, with 100% disease control rate (DCR) in patients with brain metastases [8][16] Next Steps and Future Plans - The company has selected 80 mg QD oral enozertinib as the dose for potential Phase 3 development, with ongoing enrollment and follow-up in 1L EGFR exon 20 patients [12] - A conference call and webcast is scheduled for December 6, 2025, to discuss the trial results and future plans [13]