KEY TAKEAWAYS
- ZENITH20-4 trial phase 2 (NCT03318939) aims to evaluate the efficacy and safety of poziotinib for NSCLC with HER2 exon 20 insertions.
- The study aimed to assess the efficacy and safety of the oral tyrosine kinase inhibitor poziotinib.
- ZENITH 20-4 is an open-label, phase 2 experiment with multiple cohorts and sites in which patients were given either 16 mg of poziotinib once a day (QD) or 8 mg twice daily.
- The overall response rate was 39%, the disease-free survival rate was 73%, the median DoR and PFS were 5.6 months, and poziotinib showed clinically significant effectiveness with a tolerable safety profile.
Around 2-5% of NSCLCs have mutations in the Erb-b2 receptor tyrosine kinase 2 gene (ERBB2 or HER2), most of which are insertion mutations in exon 20. Patients with HER2 exon 20 insertions in their tumors and no prior treatment for non-small cell lung cancer were evaluated for the efficacy and safety of the oral tyrosine kinase inhibitor poziotinib.
The ZENITH20 study is a worldwide, open-label, phase 2 experiment with multiple cohorts and sites. Patients with NSCLC whose tumors included HER2 exon 20 insertions were recruited in the ZENITH20-C4 study. Patients were given either 16 mg of poziotinib once a day (QD) or 8 mg twice daily (BID). Independent central assessment of the objective response rate (ORR) was the major measure of success (ICR). Disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), and safety were secondary and exploratory objectives.
In ZENITH20-C4, 80 patients were treated with either 16 mg once a day (n=47) or 8 mg twice daily (n=33). The overall response rate was 39% (95% CI, 28%-50%; 31/80), and the disease-free survival rate was 73% (95% CI, 61%-82%; 58/80). Both the median duration of response (DoR) and progression-free survival (PFS) was similar at 5.6 months (95% CI, 5.4-7.3 months). Rash (QD, 45%; BID, 39%), stomatitis (QD, 21%), and diarrhea (QD, 15%) were the most frequently reported grade 3 TRAEs. Seven patients (9%) with tumors carrying G778 P780dupGSP fared the best clinically (ORR, 71%) across all subtypes of HER2 exon 20 insertions.
For patients with treatment-naive NSCLC who carry HER2 exon 20 mutations, poziotinib showed clinically significant effectiveness with a tolerable safety profile.
Source: https://pubmed.ncbi.nlm.nih.gov/36958688/
Clinical trial:https://clinicaltrials.gov/ct2/show/NCT03318939
Cornelissen, R., Prelaj, A., Sun, S., Baik, C., Wollner, M., Haura, E. B., Mamdani, H., Riess, J. W., Cappuzzo, F., Garassino, M. C., Heymach, J. V., Socinski, M. A., Leu, S.-Y., Bhat, G., Lebel, F., Le, X., & ZENITH20-4 Investigators. (2023). Poziotinib in Treatment-Naïve Non-Small-Cell Lung Cancer Harboring HER2 Exon 20 Mutations: ZENITH20-4, A Multicenter, Multicohort, Open-label Phase 2 Trial (Cohort 4). Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer, S1556-0864(23)001995. https://doi.org/10.1016/j.jtho.2023.03.016
