Poziotinib Activity And Durability Of Responses In Previously Treated Egfr Exon 20 Nsclc Patients - A Phase 2 Study

Introduction and Purpose of Study: Effective and approved therapy for treating non-small cell lung cancer (NSCLC) with EGFR exon 20 mutations is an unmet medical need. Poziotinib is a potent tyrosine kinase inhibitor (TKI) of EGFR and HER2 exon 20 insertion mutants. We evaluated the efficacy and safety of poziotinib in previously treated NSCLC patients with EGFR exon 20 insertion mutations (ZENITH20-1) in an independent cohort of a multi-cohort, multi-center Phase 2 study. Methods: Poziotinib (16 mg) was administered orally QD, allowing dose reductions for AEs, with follow up for 24 months. The primary endpoint was objective response rate (ORR), evaluated by central radiographic review using RECIST v1.1. The ORR endpoint was to be met if the lower bound of 95% CI\u003e17% in the As-Treated Population. The secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS) and safety. Safety monitoring was conducted throughout the study. Results: A total of 115 patients with a median age of 61 years (33-83) were enrolled. Patients had received and failed prior therapy (median of 2 [1-9]) with majority receiving both chemo and immunotherapy. The median relative dose intensity was 72% (7-100%) with 65% having dose reductions. 10% of patients discontinued due to related AEs. The ORR was 14.8% (95% CI 8.9%-22.6%), and the DCR was 68.7% (95% CI 59.4%-77.0%). Seventeen patients had a confirmed partial response (PR), 5 patients had unconfirmed PR and 62 (53.9%) patients had stable disease (SD). Overall, 75 (65%) patients had tumor size reductions. The median DoR was 7.4 months (95% CI 3.7-9.7) and the median PFS was 4.2 months (95% CI 3.7-6.6). Safety profile was mechanism related and similar to other 2nd generation tyrosine kinase inhibitors with the most common treatment-related Grade ≥3 AEs (preferred term) being rash (28%), diarrhea (26%), stomatitis (9%) and paronychia (6%). The incidence of treatment-related pneumonitis, an important AE associated with TKIs, was 4%. Conclusion: Although the ORR primary endpoint was not met, poziotinib induced tumor size reduction in the majority (65%) of patients. The tumor size reduction combined with long duration of response demonstrated the clinical activity of poziotinib in treating this patient population. We are further optimizing dosing and AE management. Citation Format: Xiuning Le, Jonathan Goldman, Jeffrey Clarke, Nishan Techekmedyian, Zofia Piotrowska, David Chu, Gajanan Bhat, Francois Lebel, Mark Socinski. Poziotinib activity and durability of responses in previously treated EGFR exon 20 NSCLC patients - a Phase 2 study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT081.