Taiho Oncology, Taiho Pharmaceutical, and Cullinan Therapeutics announced that the 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) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy, with or without prior amivantamab. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of February 27, 2027.
The NDA is supported by data from the Phase 2b portion of the REZILIENT1 trial, which evaluated zipalertinib monotherapy in previously treated patients with EGFR exon 20 insertion–mutated NSCLC. REZILIENT1 met its primary endpoint of objective response rate (ORR), with study results presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in the Journal of Clinical Oncology.
In the primary efficacy population (n=176), zipalertinib achieved a confirmed ORR of 35% and a median duration of response (mDOR) of 8.8 months. Among patients who had received prior platinum-based chemotherapy only (n=125), the confirmed ORR was 40% with a mDOR of 8.8 months. Exploratory analyses showed a confirmed ORR of 30% and mDOR of 14.7 months in patients previously treated with amivantamab without other exon 20–targeted therapy (n=30), and a confirmed ORR of 31% with mDOR of 8.3 months in patients with brain metastases (n=68).
The safety profile of zipalertinib in REZILIENT1 was described as manageable and consistent with earlier data, with the most common treatment-emergent adverse events including paronychia, rash, anemia, dermatitis acneiform, diarrhea, dry skin, nausea, and stomatitis, most of which were grade 1 or 2 per CTCAE v5.0. Zipalertinib (CLN‑081/TAS6417) is an oral, irreversible EGFR tyrosine kinase inhibitor designed to selectively inhibit EGFR variants with exon 20 insertion mutations while sparing wild-type EGFR and has received FDA Breakthrough Therapy Designation for this NSCLC population.
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