CAMBRIDGE, Mass. — October 1, 2026
Cullinan Therapeutics, Inc. announced the initiation of a New Drug Application (NDA) submission to the U.S. FDA for zipalertinib in combination with platinum-based chemotherapy for previously untreated patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion (ex20ins) mutations. The submission process is being conducted under the FDA’s Real-Time Oncology Review (RTOR) program, which allows sponsors to submit clinical data ahead of the complete application to facilitate earlier regulatory review. Cullinan expects to complete the NDA submission by the end of 2026.
REZILIENT3 Supports First-Line Zipalertinib Combination
The NDA submission is supported by results from the Phase 3 REZILIENT3 study, which met its primary endpoint by demonstrating a statistically significant and clinically meaningful improvement in median progression-free survival with zipalertinib plus chemotherapy compared with chemotherapy alone. The results were presented at the 2026 World Conference on Lung Cancer during a Presidential Symposium. According to Cullinan, the combination produced the longest median progression-free survival observed to date in first-line EGFR exon20ins NSCLC. The company is pursuing the application for patients with previously untreated, locally advanced or metastatic disease.
Zipalertinib Targets EGFR Exon 20 Insertion Mutations
Zipalertinib (CLN-081/TAS6417) is an oral, irreversible EGFR inhibitor designed to target activating EGFR mutations, including exon 20 insertion mutations. EGFR exon20ins mutations represent a genetically defined subset of NSCLC and are associated with a limited number of targeted treatment options. Zipalertinib is being developed by Taiho Oncology and Taiho Pharmaceutical in collaboration with Cullinan Therapeutics in the United States. The drug remains investigational and has not been approved by any health authority.
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Cullinan Advances Zipalertinib Toward Regulatory Review
The first-line NDA submission adds to Cullinan’s ongoing regulatory development of zipalertinib. Zipalertinib has received FDA Breakthrough Therapy designation for locally advanced or metastatic EGFR exon20ins NSCLC in patients previously treated with platinum-based chemotherapy. A separate NDA seeking accelerated approval for zipalertinib monotherapy in that setting remains under FDA review, with a PDUFA target action date of February 27, 2027. Cullinan is eligible for milestone payments of $30 million and $100 million upon second-line and first-line U.S. regulatory approvals, respectively. Completion of the RTOR-enabled first-line NDA submission by year-end 2026 will advance zipalertinib into the next stage of regulatory evaluation for EGFR exon20ins NSCLC.
Source:Cullinan Therapeutics, press release
