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Translational insights and overall survival in the U31402-A-U102 study of patritumab deruxtecan (HER3-DXd) in EGFR-mutated NSCLC.
- Source :
-
Annals of Oncology . May2024, Vol. 35 Issue 5, p437-447. 11p. - Publication Year :
- 2024
-
Abstract
- Human epidermal growth factor receptor 3 (HER3) is broadly expressed in non-small-cell lung cancer (NSCLC) and is the target of patritumab deruxtecan (HER3-DXd), an antibody–drug conjugate consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. U31402-A-U102 is an ongoing phase I study of HER3-DXd in patients with advanced NSCLC. Patients with epidermal growth factor receptor (EGFR)-mutated NSCLC that progressed after EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy (PBC) who received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks had a confirmed objective response rate (cORR) of 39%. We present median overall survival (OS) with extended follow-up in a larger population of patients with EGFR -mutated NSCLC and an exploratory analysis in those with acquired genomic alterations potentially associated with resistance to HER3-DXd. Safety was assessed in patients with EGFR -mutated NSCLC previously treated with EGFR TKI who received HER3-DXd 5.6 mg/kg; efficacy was assessed in those who also had prior PBC. In the safety population (N = 102), median treatment duration was 5.5 (range 0.7-27.5) months. Grade ≥3 adverse events occurred in 76.5% of patients; the overall safety profile was consistent with previous reports. In 78/102 patients who had prior third-generation EGFR TKI and PBC, cORR by blinded independent central review (as per RECIST v1.1) was 41.0% [95% confidence interval (CI) 30.0% to 52.7%], median progression-free survival was 6.4 (95% CI 4.4-10.8) months, and median OS was 16.2 (95% CI 11.2-21.9) months. Patients had diverse mechanisms of EGFR TKI resistance at baseline. At tumor progression, acquired mutations in ERBB3 and TOP1 that might confer resistance to HER3-DXd were identified. In patients with EGFR -mutated NSCLC after EGFR TKI and PBC, HER3-DXd treatment was associated with a clinically meaningful OS. The tumor biomarker characterization comprised the first description of potential mechanisms of resistance to HER3-DXd therapy. • The phase I U31402-A-U102 study evaluated HER3-DXd in heavily pretreated patients with EGFR -mutated NSCLC. • Ninety-seven patients previously treated with EGFR TKI and PBC received HER3-DXd 5.6 mg/kg intravenously every 3 weeks. • Responses were seen across the range of HER3 expression and across diverse mechanisms of resistance to EGFR TKI therapy. • Acquired mutations in ERBB3 were characterized. • OS was 15.8 months (95% CI 10.8-21.5 months). [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09237534
- Volume :
- 35
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Annals of Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 176925256
- Full Text :
- https://doi.org/10.1016/j.annonc.2024.02.003