Treatment of non-small cell lung cancer (NSCLC) with EGFR or HER2 exon 20 mutations is a serious unmet medical need. We are evaluating the efficacy and safety of poziotinib, a potent EGFR and HER2 exon 20 tyrosine kinase inhibitor (TKI), in a large, prospective multi-cohort study (N=603). Here, we report results from a cohort of previously treated patients with advanced NSCLC exon 20 insertion mutations (ZENITH20-2 N=90).
Patients enrolled in ZENITH20-2 had HER2 exon 20 insertion mutations per a CLIA certified (or equivalent) sequencing test. Poziotinib (16 mg) was administered orally QD, allowing dose interruptions/reductions for toxicity if needed. The primary endpoint was objective response rate (ORR), evaluated centrally by an independent image review committee using RECIST 1.1 with a 95% CI pre-specified lower bound of 17%. Secondary endpoints included disease control rate, duration of response, progression-free survival, and safety.
In ZENITH20-2
ZENITH20-2 met its ORR primary efficacy endpoint with durable responses and presented a manageable safety profile, typical of 2nd generation TKIs. Additional cohorts are enrolling to explore alternative dose levels and BID dosing.
NCT03318939.
Spectrum Pharmaceuticals.
Spectrum Pharmaceuticals.
M.A. Socinski: Research grant/Funding (institution): Spectrum Pharmaceuticals. R. Cornelissen: Research grant/Funding (institution): Spectrum Pharmaceuticals. M.C. Garassino: Research grant/Funding (institution): Spectrum Pharmaceuticals. J. Clarke: Research grant/Funding (institution): Spectrum Pharmaceuticals. N. Tchekmedyian: Research grant/Funding (institution): Spectrum Pharmaceuticals. J. Molina: Research grant/Funding (institution): Spectrum Pharmaceuticals. J.W. Goldman: Research grant/Funding (institution): Spectrum Pharmaceuticals. G. Bhat: Full/Part-time employment: Spectrum Pharmaceuticals. F. Lebel: Full/Part-time employment: Spectrum Pharmaceuticals. X. Le: Research grant/Funding (institution): Spectrum Pharmaceuticals.