PDS0101 Combo Therapy Delivers Survival Boost in HNSCC for Patients With Low PD-L1

A subanalysis of final data from the phase 2 VERSATILE-002 study (NCT04260126) evaluating the combination of PDS0101 (Versamune) and pembrolizumab (Keytruda) reveals promising survival benefits among patients with head and neck squamous cell carcinoma (HNSCC) who have low PD-L1 expression (combined positive score [CPS] of 1–19).¹

Initial data, announced in 2024, indicated that the study had met its primary end point of best overall response (BOR); a final readout of data was then released in August 2025, which detailed positive survival data for the overall study population. The present analysis, which examined a subset (n = 32) of the whole cohort (n = 53), yielded a median overall survival (OS) of 29.5 months, a marked increase from previously published standard-of-care median OS data in this subgroup, where median OS with pembrolizumab monotherapy was 10.8 months, and with pembrolizumab and chemotherapy, 12.3 months.

“Patients with low levels of PD-L1 expression have typically shown poor response to immune checkpoint inhibitor [ICI] therapy, leaving [patients with] HNSCC in this subtype with few viable treatment options and a poor prognosis,” said Kirk Shepard, MD, chief medical officer of PDS Biotechnology, in a press release.¹

“This subanalysis of survival data from the CPS 1–19 patient cohort appears to show that the multifunctional T-cell immune response of PDS0101 treatment may overcome the documented limitations of [ICI] therapy and significantly improve survival in one of the most difficult-to-treat patient populations. This is a very encouraging finding, pointing to the potential of PDS0101 to improve treatment outcomes in a patient group that has historically derived limited benefit from current standards of care,” Shepard added.

What Is the VERSATILE-002 Study Investigating?

The phase 2 VERSATILE-002 study is a single-arm, open-label, multicenter study assessing the efficacy and safety of PDS0101, an investigational T-cell-stimulating and human papillomavirus 16 (HPV16)-targeted immunotherapy, plus pembrolizumab in first-line treatment of unresectable, recurrent and/or metastatic HPV16-positive HNSCC.^2,3 The objective of the study was to evaluate the combination’s impact on patients who are either naive to or refractory to ICIs.¹ For inclusion in the checkpoint-naive cohort, patients must have had a CPS of 1 or more and not have had prior immunological therapy for metastatic disease.²

As part of the therapeutic regimen, patients concurrently received 200 mg of pembrolizumab administered intravenously with 1 mL subcutaneous injections of PDS0101.³ The regimen was administered every 3 weeks during the first 4 treatment cycles with a final dose during cycle 12. Pembrolizumab monotherapy was administered during all other cycles for approximately 2 years.

The study examined BOR as its primary end point and progression-free survival, OS, and safety and tolerability as secondary end points.

What Are the Clinical Implications?

The prevalence of HNSCC has been increasing steadily over the past decade.² Amidst this rising burden, patients with low levels of PD-L1 expression are particularly affected as they are considered a difficult-to-treat population among patients with HNSCC.¹ The findings of this subanalysis demonstrate promising, well-tolerated treatment prospects for this vulnerable population without the use of chemotherapy.

However, it is important to note that no head-to-head studies have been performed comparing PDS0101 and pembrolizumab as monotherapies with the combination regimen to date. Larger, controlled trials will be necessary to evaluate the performance of this combination against other treatments and isolate the effect of the agent in treating HPV-positive HNSCC.

REFERENCES:

1. PDS Biotech Sets Significant Benchmark in Head and Neck Cancer by Achieving Extended Survival in Low PD-L1 Expression (CPS 1-19) Cohort in VERSATILE-002 Trial, Potentially Eliminating Need for Chemotherapy in the Population. News release. PDS Biotechnology. Published September 18, 2025. Accessed September 23, 2025. https://tinyurl.com/3b8fr8pe

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 September 23, 2025. https://clinicaltrials.gov/study/NCT04260126

3. 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