Cullinan Therapeutics, Taiho Pharmaceutical, and Taiho Oncology announced positive Phase 2b results from the REZILIENT1 trial of zipalertinib, an oral EGFR inhibitor, in patients with advanced or metastatic non-small cell lung cancersmall cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations who had received prior therapy. The data, presented at the 2025 ASCO Annual Meeting, showed promising overall objective response rates (ORR) and median duration of response (mDOR) across various patient subgroups, including those with prior platinum-based chemotherapy, prior amivantamab, and brain metastases. The safety profile remained consistent with previous reports, with manageable and mostly low-grade treatment-related adverse events.
These results are particularly important because EGFR exon 20 insertion mutations represent a challenging subtype of NSCLC with limited treatment options. Patients with these mutations often experience disease progression even after initial treatment with standard therapies, including amivantamab. The REZILIENT1 data suggest that zipalertinib could offer a much-needed new oral treatment option for these patients, particularly those who have progressed after other therapies. The extended mDOR observed in patients previously treated with amivantamab is especially noteworthy and indicates the potential for durable clinical benefit in a population with high unmet medical needs.
In the overall efficacy population (n=176) of the REZILIENT1 trial, the confirmed ORR was 35% with an mDOR of 8.8 months. The ORR was 40% in patients who received only prior platinum-based chemotherapy. Notably, in the subgroup of patients previously treated with chemotherapy and amivantamab, the ORR was 30% with a significantly longer mDOR of 14.7 months. Furthermore, patients with brain metastases also demonstrated a respectable ORR of 31%. The most frequently reported treatment-related adverse events were primarily dermatological (paronychia, rash, dermatitis acneiform, dry skin) and gastrointestinal (diarrhea, stomatitis), mostly Grade 1 or 2.
The positive results from the REZILIENT1 trial support further development of zipalertinib as a potential new therapy for patients with EGFR exon 20 insertion-positive NSCLC. This data could pave the way for regulatory submissions and, if approved, position zipalertinib as a valuable addition to the treatment landscape for this difficult-to-treat patient population. It could potentially change the standard of care and significantly improve outcomes for these patients.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
