Cullinan Therapeutics, Inc. filed a Current Report on Form 8-K on September 13, 2026, announcing the results of the Phase 3 REZILIENT3 clinical trial. The trial evaluated the combination of zipalertinib and chemotherapy versus chemotherapy alone as a first-line treatment for patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations.
The study enrolled a total of 279 advanced NSCLC patients who had not received prior treatment for advanced disease. After a safety lead-in of six patients, participants were randomly assigned to receive either 100 milligrams of zipalertinib twice daily plus platinum-based chemotherapy (n=140) or chemotherapy alone (n=139). Baseline characteristics, including age, sex, and the presence of brain metastases, were reported as balanced between the two arms.
At a pre-planned interim efficacy analysis following 122 progression-free survival (PFS) events, the combination of zipalertinib and chemotherapy demonstrated a statistically significant improvement in median PFS compared to chemotherapy alone. The median PFS was 14.5 months for the combination arm and 8.5 months for the control arm, with a hazard ratio of 0.50 (95% confidence interval, 0.34-0.73; P=0.00015). This benefit was observed across subgroups, including patients with brain metastases.
Objective response rates were also higher in the zipalertinib combination group (65.0%) compared to the chemotherapy-only group (40.3%). The median duration of response was 14.2 months for the combination versus 9.9 months for the control arm. At an interim overall survival analysis with 30% event maturity, the hazard ratio for death was 0.72 (95% confidence interval, 0.42-1.23).
The safety profile of the zipalertinib combination was generally consistent with the known safety profiles of the individual agents. Grade 3 or higher adverse events occurred in 87.1% of patients receiving the combination compared to 54.4% in the control arm. These higher rates were primarily due to manageable hematologic adverse events. Grade 3 or higher EGFR-related toxicities, such as rash (10.7%) and diarrhea (1.4%), were reported only in the combination arm.
