PDS0101 With Pembrolizumab in HPV16-Positive Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: A Phase 2...

The incidence of human papillomavirus type 16 (HPV16-positive) recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) is rising. Approved therapies offer a durable response to a minority of patients.

To determine the efficacy and safety of a therapeutic HPV16-targeted immunotherapy, PDS0101, in combination with pembrolizumab in participants with HPV16-positive R/M HNSCC, with separate evaluation of immune checkpoint inhibitor (ICI)-naive and ICI-resistant cohorts.

VERSATILE-002 was a phase 2, open-label, multicenter nonrandomized clinical trial conducted at 26 oncology centers from March 29, 2021, to May 15, 2025, across the US, UK, and Ireland using the Simon 2-stage optimal design. Efficacy analyses were performed on modified intent-to-treat (mITT) population; safety analyses included all participants who received 1 or more doses. Eighty-eight participants with histologically confirmed R/M HPV16-positive HNSCC were enrolled, of whom 87 (98.9%) received treatment and composed the safety population. Seventy five (85.2%) were in the mITT population used for efficacy analyses, of whom 53 (70.7%) were ICI-naive with a programmed cell death ligand 1 combined positive score of 1 or greater and 22 (29.3%) were ICI-resistant.

Pembrolizumab (200 mg, intravenously, every 3 weeks for up to 35 cycles) plus subcutaneous PDS0101 (5 scheduled doses per protocol).

The primary end point was objective response rate (ORR) per the Response Evaluation Criteria in Solid Tumors, version 1.1, by a masked independent central reviewer. Secondary end points included progression-free survival (PFS), median overall survival (mOS), and safety, with exploratory end points of duration of response, disease control rate, and response rates by programmed cell death ligand 1 status.

Of the 75 patients in the mITT population, the mean (SD) age was 64.0 (8.3) years; 4 individuals (5%) were female and 71 (95%) were male; and 2 individuals (3%) were Asian, 1 (1%) was Black, 5 (7%) were Hispanic, and 71 (95%) were White. Among 53 ICI-naive participants in the mITT cohort, ORR by the central reviewer was 34.0%, median PFS was 5.3 months (95% CI, 2.10-9.00), and mOS was 39.3 months (95% CI, 23.90 to not evaluable). Among 22 ICI-resistant patients in the mITT cohort, no objective responses were observed and the primary end point (ORR by central reviewer) was not met, but mOS was 14.8 months (95% CI, 8.50-26.00). The treatment was well tolerated, with 13.8% experiencing grade 3 or higher treatment-related adverse events.

The results of this nonrandomized clinical trial suggest that PDS0101 plus pembrolizumab showed antitumor activity in ICI-naive HPV16-positive R/M HNSCC, with favorable safety, response rates, and survival outcomes. The findings support further evaluation in a first-line setting.

ClinicalTrials.gov Identifier: NCT04260126.