Final Data from VERSATILE-002 Show Survival Benefit in HPV16-Positive HNSCC

Final topline survival data from the phase 2 VERSATILE-002 trial (NCT04260126) show that the combination of PDS0101 (Versamune HPV) and pembrolizumab (Keytruda) yielded a median overall survival (OS) of 39.3 months (95% CI, 23.9–not estimable [NE]) in patients with HPV16-positive recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) with a combined positive score (CPS) ≥1.¹ The data suggest a durable clinical effect for the combination regimen, addressing a significant unmet need in this patient population.

“We believe this final readout of topline survival data from our VERSATILE-002 clinical trial supports the durable clinical effect of PDS0101 with similarly promising survival outcomes reported in two other recently published studies, the IMMUNOCERV study and the NCI-led study in HPV16-positive recurrent and/or metastatic cancers,” said Dr. Kirk Shepard, MD, chief medical officer of PDS Biotechnology, in a press release. “We believe PDS0101, which is simple and easy to administer, brings new hope to the rapidly growing population of HPV16-positive head and neck cancer patients. We look forward to publishing the full data set for this trial later this year.”

The open-label, multicenter trial enrolled 53 patients with HPV16-positive first-line recurrent and/or metastatic HNSCC. The therapeutic regimen consisted of subcutaneous injections of PDS0101 in combination with intravenous infusions of pembrolizumab. The PDS0101 doses were administered during the first 4 treatment cycles, with a final dose on cycle 12. Pembrolizumab monotherapy was continued on alternating cycles until disease progression, death, or up to cycle 35. This therapeutic approach aimed to leverage PDS0101's ability to induce high levels of long-lasting, multifunctional HPV16-specific CD8+ T cells to enhance the efficacy of the immune checkpoint inhibitor.

The durable patient survival was similar across various patient demographics and clinical characteristics, including age, CPS status, and prior treatment history, suggesting the combination's broad applicability within this specific cohort. No patients discontinued the trial due to treatment-related adverse events, an important safety outcome that speaks to the tolerability of the combination therapy.

Data presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting previously reported a median OS for patients with CPS ≥1 of 30 months (95% CI, 23.9–NE). For the CPS ≥1 to 19 subgroup, the median OS was 29.5 months (95% CI, 15.3–NE), and for the CPS ≥20 subgroup, the median OS was 39.3 months (95% CI, 18.4–NE).²

The development of new therapeutic strategies for HPV-related HNSCC is critical. The incidence of this disease is rising, and targeted therapies that address the underlying viral etiology are urgently needed. Unlike some viral-associated cancers where the virus is a persistent, nonimmunogenic presence, HPV in HNSCC presents an opportunity for immune-based targeting.¹

PDS0101, an investigational immunotherapy, is designed to present specific HPV16 antigens to the immune system, thereby promoting a targeted antitumor immune response. When combined with pembrolizumab, an anti–PD-1 monoclonal antibody, the goal is to both activate tumor-specific T cells and remove the checkpoint blockade that allows cancer cells to evade immune surveillance.

PDS Biotech plans to publish the full dataset from the VERSATILE-002 trial later this year. It is important for clinicians to note that no head-to-head studies have been performed comparing pembrolizumab and PDS0101 as monotherapies to the combination regimen. Future research and larger trials will be necessary to further characterize the long-term efficacy and safety of this combination, as well as to compare its performance against other emerging treatments for HPV-positive HNSCC.

This article was generated with assistance from Google Gemini. It was edited and reviewed by Targeted Oncology staff. If you have any questions about the use of AI, please contact us.

REFERENCES:

1. PDS Biotech Announces Final Topline Survival Data from VERSATILE-002 Phase 2 Trial in Head and Neck Cancer. News release. PDS Biotechnology. August 25, 2025. Accessed August 25, 2025. https://tinyurl.com/n6e7a6ty

2. Weiss J, Kaczmar JM, Harrington KJ, et al. Versatile-002: Overall survival of HPV16-positive recurrent/metastatic head and neck squamous cell carcinoma patients treated with T cell stimulating immunotherapy PDS0101 and pembrolizumab. J Clin Oncol. Volume 43, Number 16_suppl. doi:10.1200/JCO.2025.43.1