The FDA has accepted the NDA for zipalertinib in previously treated EGFR exon 20 insertion–positive NSCLC, supported by REZILIENT1 data showing durable responses.
Written By: Dr. Preethi Putti, PharmD
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration (FDA) has accepted for review a New Drug Application (NDA) for zipalertinib for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy, with or without prior treatment with amivantamab. The PDUFA target action date is February 27, 2027.
Data from the REZILIENT1 trial demonstrated clinically meaningful and durable responses with zipalertinib. In the primary efficacy population (n=176), the confirmed objective response rate (ORR) was 35%, with a median duration of response (mDOR) of 8.8 months, including patients previously treated with amivantamab. Among patients treated after platinum-based chemotherapy only (n=125), ORR was 40% with a similar mDOR of 8.8 months.
In exploratory analyses, patients previously treated with amivantamab without other exon 20–targeted therapies (n=30) achieved an ORR of 30% and a mDOR of 14.7 months. Patients with brain metastases (n=68) showed an ORR of 31% and a mDOR of 8.3 months. These outcomes were assessed using standard tumor response criteria (RECIST v1.1) with independent central review.
Zipalertinib (CLN-081/TAS6417) is an oral, small-molecule inhibitor designed to selectively target EGFR exon 20 insertion mutations while sparing wild-type EGFR. The therapy has demonstrated a manageable safety profile consistent with EGFR inhibition and received Breakthrough Therapy Designation from the FDA in 2021 for patients with previously treated EGFR exon 20 insertion–positive NSCLC.
The application is supported by the ongoing Phase 1/2 REZILIENT1 (NCT04036682) trial, which is evaluating zipalertinib in patients with NSCLC harboring EGFR exon 20 insertion mutations who have received prior systemic therapies, including platinum-based chemotherapy.
Harold Keer Chief Medical Officer, Taiho Oncology emphasized that zipalertinib was developed to address unmet needs in EGFR exon 20 insertion–mutated NSCLC and described the FDA’s NDA acceptance as a key milestone, with plans to continue working closely with the FDA during the review.
Jeffrey Jones Chief Medical Officer, Cullinan Therapeutics highlighted NDA acceptance as a step toward making zipalertinib available to patients with limited options, expressed gratitude to patients and collaborators in the REZILIENT program, and noted the drug’s potential to address a significant unmet need in partnership with Taiho.
Cullinan Therapeutics A clinical-stage biopharmaceutical company collaborating with Taiho on the development of zipalertinib.
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About the Writer
Dr.Preethi Putti, PharmD is a pharmaceutical researcher with experience in healthcare and pharmaceutical market research and competitive intelligence. She specializes in analyzing drug pipelines, clinical data, and industry trends and translating complex scientific data into clear and structured medical content. Strong foundation in clinical research, data interpretation, and evidence-based healthcare analysis. Committed to advancing a global career in clinical research and healthcare innovation.