Cullinan Therapeutics, Inc. filed a Form 8-K on September 14, 2026, reporting results from the Phase 3 REZILIENT3 clinical trial evaluating zipalertinib plus chemotherapy in first-line treatment of EGFR exon 20 insertion mutation-positive non-small cell lung cancer.

Key Highlights

  • Trial enrollment: After a safety lead-in (n=6), 279 advanced NSCLC patients with EGFR ex20ins and no prior treatment for advanced disease were randomly assigned to the zipalertinib combination arm (n=140) or chemotherapy alone (n=139).
  • Median PFS: At the pre-planned interim analysis after 122 PFS events, zipalertinib plus chemotherapy produced a median PFS of 14.5 months versus 8.5 months for chemotherapy alone (hazard ratio 0.50; 95% CI, 0.34-0.73; P=0.00015).
  • Objective response rate: The combination arm achieved an objective response rate of 65.0% versus 40.3% for the control arm (P<0.0001), with median duration of response of 14.2 months versus 9.9 months.
  • Interim overall survival: At 30% maturity, the hazard ratio for death for the zipalertinib combination compared with chemotherapy alone was 0.72 (95% CI, 0.42-1.23); follow-up is ongoing.
  • Safety profile: Grade 3 or higher adverse events occurred in 87.1% of the zipalertinib combination arm versus 54.4% in the control arm, primarily hematologic in nature (58.6% vs. 28.7%).
  • Partner: Results were announced jointly with Taiho Oncology, Inc. and Taiho Pharmaceutical Co., Ltd.

REZILIENT3 Trial Data: Efficacy and Safety Findings for Zipalertinib in EGFR Ex20ins NSCLC

According to the filing, Cullinan Therapeutics and Taiho announced results from the Phase 3 REZILIENT3 trial, which evaluated zipalertinib 100 milligrams twice daily plus platinum-based chemotherapy against chemotherapy alone as a first-line treatment. Baseline characteristics were reported as balanced between arms, including age (66.5 vs. 64 years), sex (65.7% vs. 63.3% female), and brain metastases (31.4% vs. 31.7%), respectively.

The filing reported that, at the pre-planned interim efficacy analysis, the zipalertinib combination arm demonstrated significantly longer median progression-free survival than the control arm (14.5 months vs. 8.5 months; hazard ratio 0.50; 95% confidence interval, 0.34-0.73; P=0.00015). The filing noted that the PFS benefit was consistent across subgroups, including patients with brain metastases, where the hazard ratio was 0.38. The interim overall survival analysis, conducted at 30% maturity, produced a hazard ratio for death of 0.72 (95% CI, 0.42-1.23), with the filing stating that continued follow-up is ongoing to further characterize overall survival benefit and exploratory endpoints.

On safety, the filing disclosed that the observed adverse event profile of the zipalertinib combination "was generally consistent with the known safety profiles of the individual agents and no new safety signals were observed." Grade 3 or higher adverse events were reported more frequently in the combination arm (87.1% vs. 54.4%), described as primarily manageable hematologic adverse events (58.6% vs. 28.7%). Grade 3 or higher EGFR-related toxicities observed only in the zipalertinib combination arm included rash (10.7%) and diarrhea (1.4%), according to the filing. The disclosure was filed under Items 7.01 and 8.01 of the 8-K. Cullinan Therapeutics trades on NASDAQ:CGEM.

What Was Disclosed

Cullinan Therapeutics disclosed Phase 3 REZILIENT3 clinical trial results for zipalertinib plus chemotherapy in EGFR ex20ins NSCLC, including pre-planned interim PFS, objective response rate, interim overall survival data, and an adverse event profile, via an 8-K filed September 14, 2026.