On April 28, 2026 Taiho Oncology, Inc., Taiho Pharmaceutical Co., Ltd., and Cullinan Therapeutics, Inc. (Nasdaq: CGEM) reported that the U.S. Food and Drug Administration (FDA) has accepted a New Drug Application (NDA) for zipalertinib for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations whose disease has progressed on or after platinum-based chemotherapy, with or without amivantamab. The Prescription Drug User Fee Act (PDUFA) target action date is February 27, 2027.
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The NDA is supported by data from the Phase 2b part of the REZILIENT1 clinical trial of zipalertinib monotherapy in patients with NSCLC harboring EGFR ex20ins mutations who have received prior therapy. The study met its primary endpoint of objective response rate. Study results from REZILIENT1 were presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and simultaneously 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, MD, PhD, Chief Medical Officer, 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, PhD, Executive Director, Board Member, Medical Affairs, Translational Development, Clinical Development, 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, MD, MBA, Chief Medical Officer, 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."
Summary of Primary Study Results:
Zipalertinib demonstrated clinically meaningful efficacy in the primary efficacy population (n=176), including 51 patients who had received prior amivantamab.
The confirmed objective response rate (ORR) was 35%. Median duration of response (mDOR) was 8.8 months.
In patients treated after prior platinum-based chemotherapy only (n=125), ORR was 40% with a mDOR of 8.8 months.
In exploratory subgroup analyses:
Patients who had received prior amivantamab without other ex20ins-targeted therapy (n=30) showed a confirmed ORR of 30% and mDOR of 14.7 months.
Patients with brain metastases (n=68) showed a confirmed ORR of 31% and a mDOR of 8.3 months.
The safety profile of zipalertinib was manageable and consistent with previously reported data.¹ The most common treatment-emergent adverse events were paronychia, rash, anemia, dermatitis acneiform, diarrhea, dry skin, nausea and stomatitis. Most treatment-emergent adverse events were grade 1 or 2 per NCI-Common Terminology Criteria for Adverse Events (CTCAE v5.0).
Zipalertinib is an oral EGFR tyrosine kinase inhibitor. Zipalertinib received Breakthrough Therapy Designation in 2021 for the treatment of patients with locally advanced or metastatic NSCLC harboring EGFR ex20ins mutations who have previously received platinum‑based systemic chemotherapy.
About REZILIENT1
REZILIENT1 (Researching Zipalertinib in EGFR Non-Small Cell Lung Cancer Tumors) is a Phase 1/2 clinical trial (NCT04036682) to evaluate efficacy and safety of zipalertinib in adult patients with locally advanced or metastatic NSCLC harboring EGFR ex20ins mutations who have received prior therapy. Patients were treated with oral zipalertinib 100 mg twice daily. The primary endpoints were objective response rate (ORR) and duration of response (DOR) as assessed by blinded independent central review (ICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Adverse events were characterized and graded according to the NCI-Common Terminology Criteria for Adverse Events (CTCAE v5.0).
About Zipalertinib
Zipalertinib (development code: CLN-081/TAS6417) is an orally available small molecule designed to target activating mutations in EGFR. The molecule was selected because of its ability to inhibit EGFR variants with ex20ins mutations, while sparing wild-type EGFR. Zipalertinib is designed as a next generation, irreversible EGFR inhibitor for the treatment of a genetically defined subset of patients with non-small cell lung cancer. Zipalertinib has received Breakthrough Therapy Designation from the FDA for the treatment of patients with locally advanced or metastatic NSCLC harboring epidermal growth factor EGFR ex20ins mutations who have previously received platinum-based systemic chemotherapy. Zipalertinib is investigational and has not been approved by any health authority.
Zipalertinib is being developed by Taiho Oncology, Inc., and its parent company, Taiho Pharmaceutical Co., Ltd. worldwide, and in collaboration with Cullinan Therapeutics, Inc. in the U.S.
About EGFR Exon 20 Insertion Mutations
NSCLC is a common form of lung cancer and up to 4% of all cases globally have EGFR ex20ins, which makes them the third most common EGFR mutation subtype.2 In the United States, approximately 16% of patients with NSCLC harbor EGFR mutations,2 with insertions at exon 20 accounting for up to 12% of these mutations.
(Press release, Taiho, APR 28, 2026, View Source [SID1234664874])