Poziotinib Under Review for Previously Treated HER2 Exon 20 Insertion Mutation Positive NSCLC

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A PDUFA target date of November 24, 2022 has been set for the application.

The Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for poziotinib for use in patients with previously treated locally advanced or metastatic non-small cell lung cancer (NSCLC) with HER2 exon 20 insertion mutations.

The NDA includes data from Cohort 2 of the open-label phase 2 ZENITH20 clinical trial (ClinicalTrials.gov Identifier: NCT03318939), which evaluated the safety and efficacy of poziotinib, a tyrosine kinase inhibitor, in previously treated patients with HER2 exon 20 insertion mutation positive NSCLC. Study participants (n=90) received oral poziotinib 16mg once daily; the primary endpoint was objective response rate (ORR).

Results showed a confirmed ORR of 27.8% (95% CI, 18.9-38.2); partial response was observed in 25 patients, while disease control rate was reported to be 70% (95% CI, 59.4-79.2). The median duration of response was 5.1 months and median progression free survival was 5.5 months. 

Drug interruption occurred in 87% of patients, with 12% (n=11) permanently discontinuing treatment. Treatment-related serious adverse events of grade 3 or higher included rash, diarrhea, and stomatitis.

“The NDA acceptance is a major step toward advancing the treatment for patients with HER2 exon 20 insertion mutations in lung cancer,” said Tom Riga, President and Chief Executive Officer of Spectrum Pharmaceuticals. “This remains an area of high unmet medical need as there are no treatments specifically approved for these patients.”

The FDA previously granted Fast Track designation to poziotinib for this indication.

A Prescription Drug User Fee Act (PDUFA) target date of November 24, 2022 has been set for the application.


  1. Spectrum Pharmaceuticals announces acceptance of New Drug Application filing for poziotinib. News release. February 11, 2022. https://www.businesswire.com/news/home/20220211005068/en/Spectrum-Pharmaceuticals-Announces-Acceptance-of-New-Drug-Application-Filing-for-Poziotinib.
  2. Le X, Cornelissen R, Garassino M, et al. Poziotinib in non–small-cell lung cancer harboring HER2 exon 20 insertion mutations after prior therapies: ZENITH20-2 trial. Journal of Clinical Oncology. Published online November 29, 2021. doi:10.1200/JCO.21.01323