PRINCETON, N.J. — The U.S. Food and Drug Administration has accepted a New Drug Application for zipalertinib as a potential treatment for patients with locally advanced or metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations, according to Taiho Oncology Inc., Taiho Pharmaceutical Co. Ltd., and Cullinan Therapeutics Inc.
The application covers patients whose disease has progressed following platinum-based chemotherapy, with or without prior treatment with amivantamab. The FDA has set a target decision date of Feb. 27, 2027, under the Prescription Drug User Fee Act.
The filing is supported by results from the Phase 2b portion of the REZILIENT1 clinical trial, which evaluated zipalertinib as a monotherapy in previously treated patients with EGFR exon 20 insertion–mutated non-small cell lung cancer. The study met its primary endpoint, demonstrating a clinically meaningful objective response rate. Findings were presented at the 2025 American Society of Clinical Oncology annual meeting and published in the Journal of Clinical Oncology.
“Zipalertinib was discovered at Taiho Pharmaceutical Co., Ltd., and has been developed with a focus on addressing the unmet needs of patients with EGFR exon 20 insertion-mutated non-small cell lung cancer,” said Harold Keer, M.D., Ph.D., chief medical officer of Taiho Oncology. “The FDA’s acceptance of the NDA for zipalertinib is an important milestone for this program, and we look forward to working with FDA during the review process.”
“Zipalertinib is a compound created using Taiho Pharmaceutical’s proprietary drug discovery and development technologies, Cysteinomix, with the aim of delivering a new treatment option to address high unmet medical needs,” said Takeshi Sagara, Ph.D., executive director and board member overseeing medical affairs, translational development, clinical development, and discovery and preclinical research at Taiho Pharmaceutical. “The FDA’s acceptance of the NDA represents an important milestone, reflecting the scientific and clinical data accumulated to date. We will continue to work closely with Taiho Oncology, Cullinan Therapeutics and the FDA throughout the review process, with the shared goal of ultimately delivering a new treatment option to patients with non-small cell lung cancer EGFR exon 20 insertion mutations.”
“FDA acceptance of the zipalertinib NDA is an important step toward making zipalertinib available for people living with non-small cell lung cancer with EGFR exon 20 insertion mutations, who continue to face limited treatment options,” said Jeffrey Jones, M.D., MBA, chief medical officer of Cullinan Therapeutics. “We are deeply grateful to the patients and families who have participated in the REZILIENT program, and to the investigators, study teams, and advocates whose collaboration made achievement of this milestone possible. We believe zipalertinib has the potential to help address a significant unmet need, and we look forward to working with our partners at Taiho with the goal of bringing zipalertinib to patients waiting for new treatment options.”
In the trial’s primary efficacy population of 176 patients, zipalertinib achieved a confirmed objective response rate of 35%, with a median duration of response of 8.8 months. Among patients who had received only prior platinum-based chemotherapy, the response rate was 40%, with the same median duration.
Exploratory analyses showed a 30% response rate and a median duration of response of 14.7 months in patients previously treated with amivantamab but no other exon 20–targeted therapy. In patients with brain metastases, the confirmed response rate was 31%, with a median duration of response of 8.3 months.
The drug’s safety profile was described as manageable and consistent with prior data. The most common side effects included paronychia, rash, anemia, dermatitis acneiform, diarrhea, dry skin, nausea, and stomatitis, with most events classified as mild to moderate.
Zipalertinib is an oral epidermal growth factor receptor tyrosine kinase inhibitor. It previously received Breakthrough Therapy designation from the FDA in 2021 for patients with advanced non-small cell lung cancer harboring EGFR exon 20 insertion mutations who have been treated with platinum-based chemotherapy.
