Novel PDS0101 Shows Promise in Combo With Pembrolizumab in HPV16+ HNSCC

HPV-targeting immunotherapeutic PDS0101 in combination pembrolizumab may represent a new option for patients with HPV-positive recurrent or metastatic head and neck squamous cell carcinoma.

The novel type 1 interferon and CD8–positive T-cell activating immunotherapy PDS0101 plus pembrolizumab (Keytruda) showed evidence of clinical activity and acceptable safety in patients with human papillomavirus (HPV)16–positive recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), according to a prespecified interim analysis of the phase 2 VERSATILE-002 study (NCT04260126) presented during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

Among 17 checkpoint inhibitor (CPI)–naïve patients who had a combined positive score (CPS) of at least 1 and for whom imaging data were available, the overall response rate was 41.2%, comprised of 2 complete responses (11.8%) and 5 partial responses (29.4%).With a primary end point of achieving 4 or more responses, the investigators reported that the objective of the trial had been met. Achievement of an objective response was defined by radiographic tumor responses according to RECIST 1.1 criteria.

The findings were reported in poster by authors who were led by Jared Weiss, MD, of the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina.

Neither the median progression-free survival (PFS) or overall survival (OS) had been reached at the time of analysis. The 9-month PFS and OS rates were 55.2% (95% CI, 31.9%-78.4%) and 87.2% (95% CI, 70.4%-not evaluable), respectively.

“Despite durable responses, checkpoint inhibitor therapy benefits only a minority of HNSCC patients with recurrent/metastatic disease,” they wrote. “In CPI-naïve, HPV16-positive, CPS-positive patients, PDS0101 plus pembrolizumab exhibits preliminary evidence of clinical benefit in a majority of patients with an acceptable safety profile and allows continued dosing of pembrolizumab.”

Pembrolizumab is currently approved as monotherapy in this setting. PDS0101 is a liposomal nanoparticle-based vaccine that encapsulates 6 HPV16 peptides. “PDS0101 upregulates Type 1 interferons and induced high levels of polyfunctional antitumor CD8 and CD4 T cells in vivo as well as immune memory,” according to the authors.

VERSATILE-002 is being conducted in 2 groups of patients with HPV16-positive recurrent or metastatic HNSCC, both in those who are CP -naïve as well as those who are refractory to CPIs. The poster presenter herein summarized data in the CPI-naïve group.

Eligible patients are 18 years or older with histologically confirmed recurrent, metastatic, or persistent HNSCC with HPV16 infection and PD-L1 expression. Patients were also required to have adequate organ function and an ECOG performance status of 0 or 1.

Treatment consists of pembrolizumab at 200 mg intravenously every 3 weeks, plus PDS0101 delivered subcutaneously in cycles 1 through 4 and again at cycle 12. Pembrolizumab is continued until disease progression, intolerance, or up to 35 cycles. An initial safety cohort was assessed during cycle 1 and 21 days following for dose-limiting toxicity, and thereafter for safety and tolerability.

In the safety population, the median number of PDS0101 doses received was 4 (range, 1-5) and the median number of pembrolizumab doses received was 9 (range, 1-18). Median treatment duration was 2.2 months (range, 0.0-7.7) for PDS0101 and 5.9 months (range, 0.0-11.9) for pembrolizumab. No patient has required dose reductions or discontinuations of either agent.

There were no grade 3 or greater treatment-emergent adverse events (TEAEs), nor any serious TEAEs, that were attributable to either agent. The rate of grade 1 TEAEs was 15.8%, grade 2 at 42.1%, and grade 3 at 26.3%.

“Stage 1 was sufficiently successful to justify proceeding to stage 2 in CPI-naïve patients,” according to the investigators. “Stage 1 in CPI-refractory continues accrual.” Stage 2 in the CPI-naïve population will enroll a total of 37 patients, with a goal of 14 or more total objective reposes.

PDS Biotechnology Corporation has announced that the FDA has granted Fast Track designation to PDS0101 in combination with pembrolizumab.


  1. Weiss J, Chintakuntlawar A, Price KA, et al. PDS0101 a novel type 1 interferon and CD8+ T-cell activating immunotherapy in combination with pembrolizumab in subjects with recurrent/metastatic HPV16-positive head and neck squamous cell carcinoma (HNSCC). J Clin Oncol. 2022;40(suppl 16):6041. doi:10.1200/JCO.2022.40.16_suppl.6041
  2. PDS Biotechnology granted FDA fast track designation for lead candidate PDS0101. PDS Biotechnology Corporation. News release. June 2, 2022. Accessed June 7, 2022.

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