PDS0101 (HPV16-targeted immunotherapy) + pembrolizumab drives 34% ORR and 39.3-mo mOS in 1L HPV16+ R/M HNSCC

PDS0101 is a therapeutic HPV16-targeted immunotherapy designed to generate HPV16-specific T-cell responses, here combined with the PD-1 inhibitor pembrolizumab in VERSATILE-002, a Phase 2 open-label, multicenter, nonrandomized Simon two-stage trial (NCT04260126) across the US/UK/Ireland. In the efficacy mITT set (n=75), ICI-naive, PD-L1 CPS≥1 patients (n=53) achieved a centrally reviewed ORR of 34.0%, median PFS 5.3 months (95% CI, 2.10-9.00), and median OS 39.3 months (95% CI, 23.90–NE)—numerically higher OS than historical first-line pembrolizumab monotherapy in CPS≥1 disease (mOS 12.3 months; ORR ~19% in KEYNOTE-048), though cross-trial comparisons and HPV16 enrichment likely matter here. In ICI-resistant patients (n=22), ORR was 0% (primary endpoint not met) with mOS 14.8 months (95% CI, 8.50-26.00), and safety was manageable overall with 13.8% grade ≥3 treatment-related AEs.