HPV16-Targeted Vaccine PDS0101 + Pembrolizumab Pushes 1L OS to 30–39 mo in Recurrent/Metastatic HNSCC

PDS0101 (Versamune® HPV16) is a synthetic lipid nanoparticle vaccine that primes HPV16-specific CD4 and CD8 T cells. In the single-arm Phase 2 VERSATILE-002 trial (NCT04260126), it was combined with pembrolizumab (200 mg every three weeks) in 53 previously untreated patients with HPV16-positive, CPS ≥1, recurrent or metastatic HNSCC. After a median follow-up of 18.4 months, the mOS reached 30.0 months for all patients. When broken down by CPS score, mOS was 29.5 months in patients with CPS 1–19 and 39.3 months in those with CPS ≥20. These results are roughly double the Keynote-048 benchmarks for pembrolizumab alone, which reported mOS of 12.3–14.9 months. The investigator-assessed ORR was 35.8%, rising to 47.6% in patients with CPS ≥20. Disease control was achieved in 77% of patients. mPFS was 6.3 months overall, but extended to 14.1 months in the CPS ≥20 group. The DoR was 22 months overall and was not estimable in patients with high PD-L1 expression. Grade 3 or higher TRAEs occurred in 19% of patients, mainly due to injection-site reactions and fatigue. No grade 5 events were observed. Historically, the objective response rate (ORR) of pembrolizumab in the same population is approximately 20–25%.