Cambridge, Mass. — Taiho Oncology, Taiho Pharmaceutical and Cullinan Therapeutics announced Phase 3 data showing that zipalertinib plus chemotherapy significantly improved progression-free survival compared with chemotherapy alone as a first-line treatment for patients with advanced non-small cell lung cancer carrying EGFR exon 20 insertion mutations.
The results from the REZILIENT3 trial were presented at the International Association for the Study of Lung Cancer’s 2026 World Conference on Lung Cancer in Seoul, South Korea.
At a planned interim analysis, median progression-free survival was 14.5 months with zipalertinib plus chemotherapy compared with 8.5 months with chemotherapy alone. The combination reduced the risk of disease progression or death by 50%.
“The combination of zipalertinib plus platinum-based chemotherapy in the REZILIENT3 trial demonstrated a statistically significant and clinically meaningful improvement in progression-free survival for patients with advanced non-small cell lung cancer harboring EGFR exon 20 insertion mutations,” said Helena A. Yu, M.D., Thoracic Medical Oncologist at Memorial Sloan Kettering Cancer Center and study investigator.
The objective response rate was 65% with the combination compared with 40.3% with chemotherapy alone. Median duration of response was 14.2 months versus 9.9 months, respectively.
At the interim overall survival analysis, with 30% event maturity, the hazard ratio for death was 0.72 for zipalertinib plus chemotherapy compared with chemotherapy alone. Follow-up is continuing.
The trial enrolled 279 patients with advanced EGFR exon 20 insertion mutation-positive non-small cell lung cancer who had not received prior treatment for advanced disease. Patients were randomly assigned to receive zipalertinib 100 mg twice daily plus chemotherapy or chemotherapy alone.
The progression-free survival benefit was observed across subgroups, including patients with brain metastases.
“The magnitude of progression-free survival benefit, together with improvements in response rates and duration of response seen in REZILIENT3, reinforce the potential for zipalertinib plus chemotherapy to play an important role in the first-line treatment of patients with EGFR exon 20 insertion mutation NSCLC,” said Jeffrey Jones, M.D., MBA, Chief Medical Officer of Cullinan Therapeutics.
The adverse-event profile of the combination was generally consistent with the known safety profiles of the individual treatments, with no new safety signals reported.
Grade 3 or higher adverse events occurred in 87.1% of patients receiving the combination compared with 54.4% receiving chemotherapy alone. The companies said the higher rate was primarily driven by manageable hematologic adverse events. Grade 3 or higher rash occurred in 10.7% of patients in the combination group and diarrhea in 1.4%.
