PDS0101 Plus Pembrolizumab Yields Positive Survival Results in HNSCC

The median overall survival was 39.3 months with PDS0101 plus pembrolizumab in those with front-line recurrent or metastatic head and neck squamous cell carcinoma.

Topline survival results have been released from the phase 2 VERSATILE-002 trial (NCT04260126) evaluating PDS0101 (Versamune HPV) plus pembrolizumab (Keytruda) as treatment in HPV16-positive first-line recurrent and/or metastatic head and neck squamous cell cancer (HNSCC), according to a press release from the developer, PDS Biotech.¹

In patients with a confirmed positive score (CPS) of 1 or higher, the median overall survival (OS) was 39.3 months (95% CI, 23.9-not estimable [NE]). It was noted that the best published result with standard-of-care pembrolizumab or pembrolizumab plus chemotherapy was 17.9 months, although no head-to-head studies have compared pembrolizumab and PDS0101.

High levels of long-lasting, multifunctional HPV16-specific CD8-positive T cells induced by PDS0101 promoted durable patient survival; results were similar across patient demographics and clinical characteristics, including CPS status, age, and prior treatment.

“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 2 other recently published studies, the IMMUNOCERV study [NCT04580771], and the NCI-led study [NCT04287868] in HPV16-positive recurrent and/or metastatic cancers,” stated Kirk Shepard, MD, chief medical officer of PDS Biotech, in the release.¹ “We believe PDS0101, which is simple and easy to administer, brings new hope to the rapidly growing population of [patients with] HPV16-positive head and neck cancer. We look forward to publishing the full data set for this trial later this year.”

VERSATILE-002 was an open-label, multi-center phase 2 trial that evaluated the safety and efficacy of PDS0101, an HPV16-targeted immunotherapy, with pembrolizumab in unresectable, recurrent, or metastatic HPV16-positive HNSCC.² Overall, 53 patients were enrolled in the arm of those who received first-line therapy for refractory and/or metastatic disease.

Treatment consisted of PDS0101 via 2 subcutaneous injections of 0.5 mL together with pembrolizumab via intravenous infusion at 200 mg on cycles 1, 2, 3, 4, and 12; on cycles 5 to 11 and 13 to 35, the only treatment was pembrolizumab monotherapy at 200 mg.

To be included in the study, patients had to be 18 years or older with recurrent and/or metastatic measurable disease based on RECIST v1.1 criteria, adequate organ function, and an ECOG performance status of 0 or 1.

Those who were naïve to checkpoint therapy had a histologically confirmed diagnosis of HNSCC that was recurrent, metastatic, or persistent with confirmed HPV16 infection; confirmed tumor PD-L1 expression defined as a CPS of 1 or higher; and no prior receipt of any immunological therapy for metastatic disease. Those who were experienced with checkpoint therapy had a history of a histologically confirmed diagnosis of HNSCC that was recurrent, metastatic, or persistent with confirmed HPV16 infection; characterization of tumor PD-L1 expression using an FDA-approved assay; receipt of prior treatment with checkpoint inhibitors with at least 2 doses or a minimum of 6 weeks on treatment; and documented radiographically confirmed clinical progression or recurrence.

Exclusion criteria included prior therapy with an anti–PD-(L)1 therapy, anti-PD-L2 agent, or an agent directed to another stimulatory or co-inhibitor T-cell receptor that was discontinued due to a grade 3 or higher adverse event (AE); prior systemic anti-cancer therapy, including investigational agents within 30 days of beginning study treatment; a known additional malignancy that was progressing or had required active therapy within the past 3 years; known active central nervous system meningitis or carcinomatosis meningitis; severe hypersensitivity; and history of interstitial lung disease.

The trial’s primary end point was best overall response per RECIST v1.1 criteria. Secondary end points included progression-free survival, OS, and incidence of treatment-emergent AEs; additional end points were duration of response and anti-HPV16 E6 and E7 immune responses.

“With PDS0101 plus pembrolizumab, an added benefit appears to be that the combination is well tolerated, and no patients discontinued the trial due to treatment-related [AEs],” concluded Frank Bedu-Addo, PhD, president and chief executive officer of PDS Biotech.¹

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://tinyurl.com/34spcfde
2. Study of PDS0101 and pembrolizumab combination I/​O in subjects with HPV16 + recurrent and/​or metastatic HNSCC (VERSATILE002). ClinicalTrials.gov. Updated December 18, 2024. Accessed August 25, 2025. https://tinyurl.com/2axd32ff