PDS0101/Pembrolizumab Yields 39.3-Month Median OS in HPV16-Positive HNSCC

The HPV16-targeted immunotherapy PDS0101 combined with pembrolizumab (Keytruda) produced a central review-assessed objective response rate (ORR) of 33.96% (95% CI, 21.52%-48.27%) and a median overall survival (OS) of 39.3 months (95% CI, 23.90-not evaluable [NE]) among patients with immune checkpoint inhibitor (ICI)–naive, HPV16-positive recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), according to results from the phase 2 VERSATILE-002 trial (NCT04260126) published in JAMA Oncology.¹ A separate ICI-resistant cohort had no objective responses and did not meet its primary end point.

What were the results in the ICI-naive cohort?

Among 53 ICI-naive patients in the modified intent-to-treat (ITT) population, central review identified 6 complete responses and 12 partial responses. The investigator-assessed ORR was 35.85% (95% CI, 23.14%-50.20%). The disease control rate was 60.4%, and the median duration of response was not evaluable (NE; 95% CI, 6.9 months-NE). Tumor reductions of more than 90% occurred in 22.6% of patients.

The median progression-free survival (PFS) was 5.3 months (95% CI, 2.10-9.00) by central review. At a median follow-up of 24.4 months (IQR, 9.7-29.5), the 12- and 24-month OS rates were 78.5% (95% CI, 64.5%-87.5%) and 67.6% (95% CI, 52.5%-78.8%), respectively. In an exploratory analysis, patients with a PD-L1 combined positive score (CPS) of 1 to 19 had a median OS of 29.5 months.

How effective was the regimen in the ICI-resistant cohort?

Among 22 patients in the ICI-resistant cohort, no objective responses were observed. The median PFS was 2.0 months (95% CI, 1.4-2.1), and the median OS was 14.8 months (95% CI, 8.5-26.0). The investigators wrote that this finding is consistent with evidence that ICIs are most effective when given early. Later on, tumors may lose the antigen presentation machinery that both pembrolizumab and PDS0101 depend on.

What was the safety profile of PDS0101 plus pembrolizumab?

In the ICI-naive safety population of 62 patients, 17.7% experienced grade 3 or 4 treatment-related adverse events (TRAEs). One grade 4 event, encephalitis, occurred approximately 1 year after the last PDS0101 dose and was deemed related to pembrolizumab but unrelated to PDS0101. No grade 5 TRAEs occurred. Across all 87 treated patients, the rate of grade 3 or higher TRAEs was 13.8%.

The most common TRAEs in the ICI-naive cohort were injection site pain (59.7%), fatigue (40.3%), and injection site swelling (30.6%). All injection site reactions were grade 1 or 2. AEs led to discontinuation of PDS0101 in 6.5% of patients and of pembrolizumab in 11.3%.

What is the VERSATILE-002 trial design?

The open-label, multicenter trial used a Simon 2-stage design and enrolled 88 patients across 26 centers in the US, UK, and Ireland between March 2021 and May 2025. ICI-naive patients were required to have a PD-L1 CPS of 1 or greater. ICI-resistant patients had disease progression after at least 8 weeks of prior ICI therapy.

Patients received pembrolizumab at 200 mg intravenously every 3 weeks for up to 35 cycles, plus subcutaneous PDS0101 at 1 mL on cycles 1, 2, 3, 4, and 12. The primary end point was ORR per RECIST v1.1 by masked independent central review. Secondary end points included PFS, OS, and safety.

PDS0101 combines a T cell–activating lipid platform with HPV16 E6 and E7 multiepitope peptides. It is designed to induce HPV16-specific CD4 and CD8 T-cell responses.

What are the next steps for PDS0101 in head and neck cancer?

The investigators concluded that the findings support further evaluation of the combination in the first-line setting.

“These results support the durable clinical effect of PDS0101, consistent with promising survival outcomes reported in 2 other recently published studies, the IMMUNOCERV study [NCT04580771], and the NCI-led study in HPV16-positive recurrent and/or metastatic cancers,” said Kirk Shepard, MD, chief medical officer of PDS Biotech, in a press release on the VERSATILE-002 findings.²

References

1. 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
2. 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. News release. PDS Biotechnology Corporation. September 22, 2026. Accessed September 28, 2026. https://tinyurl.com/yuh9yzeb