Effective treatment of patients with metastatic non-small cell lung cancer (mNSCLC) harboring EGFR or HER2 exon 20 insertion mutations represents a critical unmet need. Poziotinib is a potent, irreversible, tyrosine kinase inhibitor (TKI) being studied in a multi-cohort phase II study (ZENITH20). Poziotinib half-life of 7.2 hours and pharmacokinetic modeling suggests an opportunity to improve tolerability with a twice daily (BID) dosing schedule. Here we present efficacy data from once daily (QD) in treatment naïve patients as well as an exploratory study of BID dosing.
ZENITH20-3 enrolled treatment-naïve mNSCLC patients with EGFR exon 20 mutations at 16mg QD. Patients were treated until death, progression or significant toxicity. ZENITH20-5 treated patients with EGFR or HER2 exon 20 mutations in randomized arms of 10, 12, 16 mg QD or 6 and 8 mg BID. The endpoints were objective response rate (ORR per RECIST 1.1), duration of response (DOR), progression-free-survival (PFS) and safety.
In ZENITH20-3 (N=79), the median time of follow up was 9.2 months with 12 patients still receiving treatment. The intent-to-treat analysis showed an ORR of 27.8% (22/79; 95% CI: 18.4 – 39.1%) and disease control rate of 86.1%. 91% of all study patients had tumor reduction. The median DOR was 6.5 months and the median PFS was 7.2 months. Adverse event profile was similar to 2nd generation EGFR TKIs with ≥ grade 3 rash of 33% and diarrhea of 23%. Preliminary data from ZENITH20-5 (N=40) randomized cohorts of QD vs BID dosing (16mg QD vs 8mg BID; 12mg QD vs and 6mg BID) indicate that the expected AE rate was lower with BID dosing (31% vs. 21% and 27% vs. 16% respectively) in cycle 1. BID dosing schedules resulted in the relative reduction in dose interruptions by 38% and 52% respectively. Updated safety, tolerability and preliminary efficacy data will be presented.
Poziotinib demonstrated clinically meaningful activity in treatment-naïve mNSCLC patients with EGFR exon 20 mutations at 16 mg QD dosing. Preliminary data demonstrates improved tolerability and safety with BID dosing strategy and warrants further evaluation.
Clinical trial identification
Legal entity responsible for the study
Spectrum Pharmaceuticals, Inc.
Spectrum Pharmaceuticals, Inc.
A. Sacher: Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Amgen; Honoraria (institution), Advisory/Consultancy: Merck; Honoraria (institution): Pfizer; Honoraria (institution), Advisory/Consultancy: Bayer; Honoraria (institution), Advisory/Consultancy: Genentech-Roche; Honoraria (institution), Advisory/Consultancy: Kisoji; Honoraria (institution), Advisory/Consultancy: BMS; Honoraria (institution): Tesaro. X. Le, M. Socinski, M.C. Garassino: Research grant/Funding (institution): Spectrum Pharmaceuticals. J. Clarke: Advisory/Consultancy: Spectrum Pharmaceuticals. G. Bhat, F. Lebel: Full/Part-time employment: Spectrum Pharmaceuticals. All other authors have declared no conflicts of interest.