PDS0101 Plus Pembrolizumab Yields Durable Survival Benefit in HPV16+ HNSCC

Versamune HPV (formerly PDS0101) in combination with pembrolizumab (Keytruda) generated a median overall survival (OS) of 39.3 months (95% CI, 23.9-not evaluable [NE]) in patients with HPV16-positive recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) with a combined positive score (CPS) of at least 1, according to final topline results from the single-arm phase 2 VERSATILE-002 trial (NCT04260126).¹

These findings represent an improvement compared with historically published outcomes of 17.9 months with pembrolizumab alone or in combination with chemotherapy in this population, according to a news release. The durable survival outcome was supported by high levels of long-lasting, multifunctional, HPV16-specific CD8-positive T cells induced by Versamune HPV. Investigators reported that survival outcomes were consistent across patient demographics and clinical characteristics, including age, CPS status, and prior treatment.

“We believe this final readout of topline survival data from our VERSATILE-002 clinical trial supports the durable clinical effect of [Versamune HPV], with similarly promising outcomes reported in other studies,” Kirk Shepard, MD, chief medical officer of PDS Biotech, stated in the news release. “We look forward to publishing the full dataset later [in 2025].”

The VERSATILE-001 trial is an open-label, multicenter study designed to assess the safety and efficacy of Versamune HPV in combination with pembrolizumab in patients with unresectable, recurrent, or metastatic HPV16-positive HNSCC. In total, 53 patients were enrolled in the first- line recurrent/metastatic HNSCC arm of VERSATILE-002. Patients received subcutaneous Versamune HPV injections alongside pembrolizumab intravenous infusions during the first 4 treatment cycles. A fifth and final Versamune HPV dose was administered at cycle 12, with pembrolizumab monotherapy continuing every other cycle through cycle 35 or until disease progression or death.

Previously presented data from the 2025 ASCO Annual Meeting showed that at a median follow-up of 18.4 months (range, 0.2-42.7), the median OS among patients with a CPS of at least 1 (n = 53), between 1 and 19 (n = 32), and at least 20 (n = 21) was 30 months (95% CI, 23.9-NE), 29.5 months (95% CI, 15.3-NE), and 39.3 months (95% CI, 18.4-NE).² The overall response rates in these respective arms were 35.8%, 28.1%, and 47.6%. Furthermore, in the population of patients with a CPS of at least 1, the disease control rate was 77.4%, the median duration of response was 21.8 months (95% CI, 11.5-NE), and the median progression-free survival was 30.0 months (95% CI, 23.9-NE).

No patients discontinued treatment in VERSATILE-002 due to treatment-related adverse effects (TRAEs).¹ The most commonly reported TRAEs included injection site reactions (74.2%), fatigue (38.7%), headache (19.4%), pruritus (14.5%), diarrhea (12.9%), rash (9.7%), pain (8.1%), increased alanine aminotransferase levels (8.1%), and arthralgia (8.1%).² The rate of grade 3 TRAEs was 16.1%, 1 patient experienced a grade 4 TRAE, and no patients experienced grade 5 TRAEs.

“HPV16-positive head and neck cancer represents one of the fastest-growing cancer segments in the United States and Europe, yet treatment options remain limited,” Frank Bedu-Addo, PhD, president and chief executive officer of PDS Biotech, added in the news release.¹ “These results suggest that [Versamune HPV] plus pembrolizumab may offer patients both survival benefit and tolerability, and we are well positioned to advance this therapy further.”

The phase 3 VERSATILE-003 trial (NCT06790966) is ongoing. This trial is investigating Versamune HPV plus pembrolizumab vs pembrolizumab alone in the first-line setting in patients with HPV16-positive recurrent or metastatic HNSCC.³

References

1. PDS Biotech announces final topline survival data from VERSATILE-002 phase 2 trial in head and neck cancer. News release. PDS Biotech. August 25, 2025. Accessed August 25, 2025. https://pdsbiotech.com/index.php/investors/news-center/press-releases/press-releases1/132-2025-news/1016-pds-biotech-announces-final-topline-survival-data-fromvers2025-08-25-053503
2. Weiss J, Kaczmar J, Harrington K, 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. 2025;43(suppl 16):6037. doi:10.1200/JCO.2025.43.16_suppl.6037
3. Price KAR, Harrington KJ, Worden FP, et al. VERSATILE-003: a phase 3, randomized, open-label trial of PDS0101 and pembrolizumab compared with pembrolizumab for first-line treatment of patients with HPV16-positive recurrent/metastatic head and neck squamous cell carcinoma. J Clin Oncol. 2025;43(suppl 16):TPS6111. doi:10.1200/JCO.2025.43.16_suppl.TPS6111