Enfortumab vedotin plus pembrolizumab as first-line treatment in recurrent or metastatic head and neck squamous cell carcinoma: results from EV-202 cohort 9.

Abstract

To assess safety and efficacy of enfortumab vedotin (EV) and pembrolizumab as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). In this open-label, multicohort, phase 2 study (NCT04225117), the R/M HNSCC cohort (cohort 9) received EV (1.25 mg/kg IV) on days 1, 8 and pembrolizumab (200 mg IV) on day 1 in 21-day cycles. Eligible patients had R/M HNSCC, programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1, and no prior systemic therapy in R/M setting. Primary endpoint was investigator-assessed confirmed objective response rate (cORR) per RECIST v1.1. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. The primary analysis included 41 patients. Of these, 39.0% had PD-L1 CPS 1-19 and 61.0% had CPS ≥20. Median (IQR) nectin-4 expression H-score was 185.0 (110.0-255.0). In patients with oropharyngeal squamous cell carcinoma (n=14), 78.6% had p16-positive disease. Median follow-up for OS was 11.0 months. Sixteen patients achieved a response and cORR was 39.0% (95% CI: 24.2-55.5). Complete response rate was 9.8%. DOR was not estimable, and estimated 6-month DOR rate was 81.7% (95% CI: 42.0-95.4). Median PFS was 5.1 months (95% CI: 3.5-NE). Grade 3 treatment-related adverse events were reported in 41.5% of patients; most commonly, maculopapular rash (7.3%). EV with pembrolizumab demonstrated promising clinical activity as first-line treatment in patients with PD-L1 CPS ≥1 R/M HNSCC. Safety results reinforced the manageable tolerability profile of EV with pembrolizumab.