FDA accepts NDA for zipalertinib to treat advanced NSCLC with EGFR exon 20 insertion mutations
Wednesday, April 29, 2026
The U.S. Food and Drug Administration 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 mutations.
The application has been submitted by Taiho Oncology, Taiho Pharmaceutical, and Cullinan Therapeutics. It targets patients whose disease has progressed following platinum-based chemotherapy, with or without prior treatment using amivantamab. The Prescription Drug User Fee Act (PDUFA) target action date has been set for 27 February 2027.
The NDA 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 NSCLC carrying EGFR exon 20 insertion mutations. The study met its primary endpoint of objective response rate. Findings were presented at the American Society of Clinical Oncology Annual Meeting 2025 and published in the Journal of Clinical Oncology.
In the primary efficacy population of 176 patients, zipalertinib demonstrated an objective response rate (ORR) of 35%, with a median duration of response (mDOR) of 8.8 months. Among patients who had received only prior platinum-based chemotherapy, the ORR was 40%, with a similar mDOR of 8.8 months.
Subgroup analysis showed an ORR of 30% and mDOR of 14.7 months in patients previously treated with amivantamab but no other targeted therapies. In patients with brain metastases, the ORR was 31% with a mDOR of 8.3 months.
The safety profile of zipalertinib was reported as manageable and consistent with earlier findings. The most common side effects included paronychia, rash, anaemia, acneiform dermatitis, diarrhoea, dry skin, nausea and stomatitis. Most adverse events were mild to moderate in severity.
Zipalertinib is an oral EGFR tyrosine kinase inhibitor. It previously received Breakthrough Therapy Designation in 2021 for patients with advanced NSCLC with EGFR exon 20 insertion mutations who had already been treated with platinum-based chemotherapy.
Source: businesswire.com
