Updated data from the phase 2 VERSATILE-002 trial, presented at the 2024 ESMO Congress, indicate that adding Versamune HPV (PDS0101) to standard pembrolizumab (Keytruda) may lead to robust and durable responses in patients with human papillomavirus (HPV)16–positive recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The study suggests the regimen is well-tolerated and produces high clinical activity, potentially improving survival outcomes in the first-line setting.
Promising Survival Outcomes
At a data cutoff of May 17, 2024, and a median follow-up of 16 months, patients with a combined positive score (CPS) of 1 or higher (n = 53) achieved a median overall survival (OS) of 30 months (95% CI, 19.7-not evaluable) and a median progression-free survival (PFS) of 6.3 months. The objective response rate (ORR) was 35.8%, with 9.4% complete responses, and the disease control rate (DCR) was 77.4%. Notably, 21% of patients experienced tumor shrinkage between 90% and 100%. Twenty-seven patients continue to be followed for survival, 10 of whom remained on study treatment at the time of this analysis.
Safety Profile
Regarding safety, only 9 patients reported grade 3 or higher treatment-related adverse effects. According to Jared Weiss, MD, a professor of medicine at the University of North Carolina (UNC) School of Medicine, the safety profile mirrors what is expected from pembrolizumab alone, with the addition of mostly mild, grade 1 or 2 injection site reactions.
Future Directions
These findings support the continued evaluation of Versamune HPV plus pembrolizumab in the phase 3 VERSATILE-003 study, which will compare the regimen with pembrolizumab monotherapy in HPV16-positive HNSCC. "One exciting thing about the data presented here was that the survival improvement was not just in the median; the tail of the [OS] curve was substantially raised. If that is confirmed in the phase 3 study, it would change the SOC for recurrent metastatic disease and introduce a conversation about cure rate in this previously incurable [disease],” said Weiss.
Unmet Needs in HPV-Driven HNSCC
Despite advancements in treating locally advanced HPV-driven HNSCC, the increasing incidence of these cancers due to slow vaccination uptake means there is still a significant unmet need for better therapeutics in the recurrent metastatic setting. Viral-induced cancers offer a unique therapeutic vulnerability through cancer-associated neoantigens, making therapeutic vaccines like Versamune HPV a promising approach. Versamune HPV comprises peptides against HPV16 E6 and E7, combined with the adjuvant R-DOTAP.
VERSATILE-002 Trial Design
VERSATILE-002 was a single-arm, nonrandomized phase 2 study comprising standard-of-care pembrolizumab with the added therapeutic vaccine product for cancers that were both PD-L1–positive and HPV16-positive. The primary endpoint of the study was response rate, which was met and has been previously reported. The ESMO 2024 presentation focused on survival outcomes, with an impressive overall survival of 30 months.
