CAMBRIDGE, Mass. — Taiho Oncology and Cullinan Therapeutics announced the publication of promising results from their Phase 1/2 REZILIENT1 trial evaluating zipalertinib (CLN-081/TAS6417) in patients with non-small cell lung cancer (NSCLC) carrying EGFR exon 20 insertion mutations. The findings appear in the latest edition of the Journal of Clinical Oncology and will be presented at the 2025 ASCO Annual Meeting.
The REZILIENT1 study enrolled patients with EGFR ex20ins-positive NSCLC who had previously undergone treatment, including platinum-based chemotherapy and, in some cases, the EGFR-MET bispecific antibody amivantamab.
In the primary efficacy population (n=176), zipalertinib demonstrated an objective response rate (ORR) of 35.2%, with a median duration of response (mDOR) of 8.8 months and median progression-free survival (PFS) of 9.4 months. Among patients who had only received prior platinum-based chemotherapy (n=125), the ORR was higher at 40%.
The safety profile of zipalertinib was deemed manageable and aligned with earlier data. Notably, patients who had received amivantamab but no other targeted therapies had an ORR of 30% and a median response duration of 14.7 months. Patients with brain metastases also responded, showing an ORR of 30.9% and mDOR of 8.3 months.
“Despite treatment advances, there are few oral targeted therapies available for patients with EGFR ex20ins-mutated NSCLC,” said Dr. Zofia Piotrowska, the study’s lead investigator and a lung cancer specialist at Massachusetts General Hospital. “These results support zipalertinib as a promising option for patients with previously treated recurrent or metastatic disease.”
The data add to growing evidence that zipalertinib may offer a viable oral treatment alternative for a difficult-to-treat subset of lung cancer patients, with further clinical development anticipated.
