PDS0101 Plus Pembrolizumab Shows 39.3-Month Median Overall Survival in HPV16-Positive R/M HNSCC

PDS0101, an HPV16-targeted T-cell immunotherapy, combined with pembrolizumab produced a 39.3-month median overall survival (OS) in immune checkpoint inhibitor (ICI)-naive patients with HPV16-positive recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), according to Phase 2 VERSATILE-002 results published in JAMA Oncology on September 17, 2026.

PDS0101 Targets HPV16 Tumor Antigens

HPV16 is the predominant HPV genotype in HPV-associated oropharyngeal cancers and accounts for approximately 80% to 90% of HPV-positive cases. However, outcomes remain limited after disease becomes recurrent or metastatic.

PDS0101 combines a T-cell activating cationic lipid platform with multiepitope peptides derived from the HPV16 E6 and E7 proteins. The therapy promotes antigen processing and presentation through major histocompatibility complex class I and II pathways, stimulating multifunctional CD4 and CD8 T-cell responses, including memory T cells. When combined with pembrolizumab, PD-1 blockade may help sustain these tumor-specific immune responses.

VERSATILE-002 Reported Activity in ICI-Naive Disease

VERSATILE-002 (NCT04260126) was an open-label, multicenter Phase 2 trial conducted at 26 centers across the US, UK, and Ireland between March 2021 and May 2025. The study enrolled 88 patients with histologically confirmed HPV16-positive R/M HNSCC; 87 received treatment and formed the safety population, while 75 entered the modified intention-to-treat (mITT) efficacy population. This included 53 ICI-naive patients with PD-L1 combined positive score (CPS) of at least 1 and 22 patients with ICI-resistant disease.

Patients received pembrolizumab 200 mg intravenously every three weeks for up to 35 cycles, together with five scheduled subcutaneous doses of PDS0101 administered during cycles 1, 2, 3, 4 and 12.

Among the 53 ICI-naive patients, independent central review identified six complete responses and 12 partial responses, producing an objective response rate (ORR) of 34.0% (18/53; 95% CI, 21.5%-48.3%). Investigator assessment reported an ORR of 35.9%, including five complete and 14 partial responses. Median progression-free survival was 5.3 months, while median OS reached 39.3 months (95% CI, 23.9 to not evaluable).

The 12- and 24-month OS rates were 78.5% and 67.6%, respectively. Median duration of response was not reached by central review, with the 95% CI beginning at 6.9 months.

The study met its prespecified primary endpoint in the ICI-naive cohort. However, the authors emphasized that comparisons with historical pembrolizumab studies should be interpreted cautiously because VERSATILE-002 was single-arm and enrolled a selected HPV16-positive, PD-L1 CPS ≥1 population.

Safety Profile Remained Manageable

Across the safety population, 13.8% of patients experienced grade 3 or higher treatment-related adverse events. Injection-site reactions were the most characteristic adverse events, including pain, swelling and discoloration, and were grade 1 or 2. One grade 4 encephalitis event occurred approximately one year after the final PDS0101 dose and was considered unrelated to PDS0101 but related to pembrolizumab. No grade 5 treatment-related adverse events occurred.

ICI-Resistant Cohort Did Not Meet Its Response Endpoint

The activity was substantially different in patients whose disease had progressed on prior ICI therapy. Among 22 ICI-resistant patients, no objective responses were observed. Median PFS was 2.0 months and median OS was 14.8 months. The prespecified ORR endpoint was therefore not met in this cohort.

The investigators noted that these findings support evaluating the combination earlier in treatment, before mechanisms of immune escape and loss of antigen-presentation capacity become established.

Development Moves Toward First-Line Evaluation

The investigators concluded that the Phase 2 findings support confirmatory testing of PDS0101 with pembrolizumab in the first-line R/M setting. The study’s nonrandomized design, small cohort size and differences from historical trial populations remain important limitations, and the authors cautioned against interpreting cross-trial survival comparisons as direct evidence of comparative efficacy.

Separately, PDS Biotech has stated that it continues to prioritize development of PDS0301 in metastatic colorectal cancer while pursuing a partnership strategy for PDS0101. The company recently disclosed a PIPE financing of up to $22.3 million led by Nant Capital, alongside a one-year exclusive negotiation right for NantWorks to pursue an exclusive license to PDS0101.

Reference

PDS Biotech Announces Publication of VERSATILE-002 Phase 2 Clinical Trial Results of PDS0101 with pembrolizumab in HPV16-Positive Recurrent and/or Metastatic (R/M) Head and Neck Cancer in JAMA Oncology, PDS Biotechnology, 22 September 2026

Weiss J, Kaczmar J, Chintakuntlawar A, et al. PDS0101 With Pembrolizumab in HPV16-Positive Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: A Phase 2 Nonrandomized Clinical Trial. JAMA Oncol. Published online September 17, 2026. doi:10.1001/jamaoncol.2026.3492

Study of PDS0101 and Pembrolizumab Combination I/​O in Subjects With HPV16 + Recurrent and/​or Metastatic HNSCC (VERSATILE002), ClinicalTrials.gov ID NCT04260126