Multinational phase 2 trial of PDS0101 with pembrolizumab for HPV16-positive recurrent/metastatic head and neck squamous cell carcinoma

The incidence of HPV16-positive recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is rising. Approved therapies offer a durable response to a minority of patients. PDS0101 is a therapeutic HPV16-targeted immunotherapy. The phase 2 VERSATILE-002 trial, at 26 centers in the US, UK, and Ireland, evaluated the combination of PDS0101 and pembrolizumab for HPV16-positive R/M HNSCC. Partipicants received intravenous pembrolizumab 200 mg every 3 weeks for up to 35 cycles plus subcutaneous PDS0101 (5 scheduled doses per protocol). The primary endpoint was objective response rate (ORR). Eighty-eight participants were enrolled, of whom 87 received treatment and composed the safety population. Seventy-five were in the mITT population used for efficacy analyses, of whom 53 (70.7%) were immune checkpoint inhibitor (ICI)-naïve with a PD-L1 combined positive score of 1 or greater, and 22 (29.3%) were ICI-resistant. Among the ICI-naïve participants in the mITT cohort, ORR by central review was 34.0%, median progression-free survival was 5.3 months (95% CI 2.10-9.00), and median overall survival was 39.3 months (23.90-NE). Among ICI-resistant participants, no objective responses were observed, but median overall survival was 14.8 months (95% CI 8.50-26.00). Treatment was well tolerated, with 13.8% experiencing grade 3 or higher treatment-related adverse events. The authors conclude that these results suggest that PDS101 plus pembrolizumab showed antitumor activity in ICI-naïve HPV16-positive R/M HNSCC, with favorable safety, response rates, and survival outcomes.