Enfortumab Vedotin plus Pembrolizumab as First-line Treatment in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Results from EV-202 Cohort 9.

purposeTo assess the 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). PATIENTS AND

methodsIn this open-label, multicohort, phase II study (NCT04225117), the R/M HNSCC cohort (cohort 9) received EV (1.25 mg/kg IV) on days 1 and 8 and pembrolizumab (200 mg IV) on day 1 in 21-day cycles. Eligible patients had R/M HNSCC, programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥1, and no prior systemic therapy in the R/M setting. The primary endpoint was the investigator-assessed confirmed objective response rate (cORR) per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

resultsThe primary analysis included 41 patients. Of these, 39% had PD-L1 CPS 1-19, and 61% had CPS ≥20. The median interquartile range nectin-4 expression H score was 185 (110-255). In patients with oropharyngeal squamous cell carcinoma (n = 14), 78.6% had p16-positive disease. The median follow-up for OS was 11 months. Sixteen patients achieved a response, and cORR was 39% [95% confidence interval (CI), 24.2-55.5]. The complete response rate was 9.8%. Median DOR was not estimable, and the estimated 6-month DOR rate was 81.7% (95% CI, 42-95.4). The median PFS was 5.1 months (95% CI, 3.5-not estimable). Grade ≥3 treatment-related adverse events were reported in 41.5% of patients, most commonly maculopapular rash (7.3%).

conclusionsEV 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.