Poziotinib in Treatment-Naive NSCLC Harboring HER2 Exon 20 Mutations: ZENITH20-4, A Multicenter, Multicohort, Open-Label, Phase 2 Trial (Cohort 4)

Authors

Robin Cornelissen
Arsela Prelaj
Sophie Sun
Christina Baik
Mirjana Wollner
Eric B Haura
Hirva Mamdani
Jonathan W Riess
Federico Cappuzzo
Marina C Garassino
John V Heymach
Mark A Socinski
Szu-Yun Leu
Gajanan Bhat
Francois Lebel
Xiuning Le
ZENITH20-4 Investigators

Publication Date

8-1-2023

Journal

Journal of Thoracic Oncology

DOI

10.1016/j.jtho.2023.03.016

PMID

36958688

Abstract

Introduction: ERBB2 or HER2 alterations are found in approximately 2% to 5% of NSCLCs; most are exon 20 insertion mutations. The efficacy and safety of poziotinib, an oral tyrosine kinase inhibitor, were assessed in patients with treatment-naive NSCLC whose tumors harbor HER2 exon 20 insertions.

Methods: ZENITH20 is an open-label, multicohort, multicenter, global, phase 2 trial. ZENITH20-C4 enrolled treatment-naive patients with NSCLC with tumors harboring HER2 exon 20 insertions. Poziotinib was administered 16 mg once daily (QD) or 8 mg twice daily (BID). The primary end point was objective response rate (ORR) by independent central review. Secondary and exploratory end points included disease control rate, duration of response, progression-free survival, and safety.

Results: A total of 80 patients (16 mg QD, n = 47; 8 mg BID, n = 33) were treated in ZENITH20-C4. ORR was 39% (95% confidence interval [CI]: 28%-50%; 31 of 80), with a disease control rate of 73% (95% CI: 61%-82%; 58 of 80); 80% of the patients experienced tumor reduction. Median duration of response was 5.7 (95% CI: 4.6-11.9) months, and median progression-free survival was 5.6 (95% CI: 5.4-7.3) months. The most common grade 3 treatment-related adverse events were rash (QD, 45%; BID, 39%), stomatitis (QD, 21%; BID, 15%), and diarrhea (QD, 15%; BID, 21%). Among all subtypes of HER2 exon 20 insertions, seven patients (9%) harboring tumors with G778_P780dupGSP had the best clinical outcomes (ORR, 71%).

Conclusions: Poziotinib was found to have clinically meaningful efficacy with a manageable toxicity profile for patients with treatment-naive NSCLC harboring HER2 exon 20 mutations.

Keywords

Humans, Lung Neoplasms, Mutation, Carcinoma, Non-Small-Cell Lung, Protein Kinase Inhibitors, Exons, Exon 20 mutations, HER2, Non–small cell lung cancer (NSCLC), Poziotinib, Tyrosine kinase inhibitor

Published Open-Access

yes

Recommended Citation

Cornelissen, Robin; Prelaj, Arsela; Sun, Sophie; et al., "Poziotinib in Treatment-Naive NSCLC Harboring HER2 Exon 20 Mutations: ZENITH20-4, A Multicenter, Multicohort, Open-Label, Phase 2 Trial (Cohort 4)" (2023). Faculty, Staff and Student Publications. 4477.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4477