FDA Grants Fast Track Designation to PDS0101/Pembrolizumab Combination for HPV16+ Recurrent or Metastatic Head and Neck Cancer


The FDA has granted PDS0101 Fast Track Designation for use in combination with pembrolizumab in patients with recurrent or metastatic HPV16-positive head and neck cancer.

According to an announcement by PDS Biotechnology Corporation, the FDA has granted PDS0101 Fast Track Designation for use in combination with pembrolizumab (Keytruda) in patients with recurrent or metastatic HPV16-positive head and neck cancer.1

The doublet is currently being tested in an open, multi-centre, Phase 2 VERSATILE-002 study (NCT04260126) in which it was shown to have preliminary evidence of clinical activity and a favorable toxicity profile in most patients with checkpoint inhibitor-naïve human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC).2

“We are thrilled that the FDA has recognized PDS0101 in combination with Fast Track designation [pembrolizumab]said Frank Bedu-Addo, chief executive officer of PDS Biotechnology Corporation, in a press release. “The prevalence of HPV-associated head and neck cancer continues to rise, leaving only limited treatment options available to this affected group. This award underscores the potential of the Versamune® platform and the need for a new therapy that could improve outcomes in this devastating disease.”

T-cell and HPV-targeted immunotherapy upregulates type 1 interferons and elicits high levels of polyfunctional antitumor CD8+ and CD4+ T cells and immune memory in vivo. These HPV-specific T cells can target anal, cervical, head and neck, penile, vaginal, and vulvar cancers caused by HPV16 infection.

The investigational agent was found to exhibit antitumor synergy when combined with checkpoint inhibitors. Researchers have hypothesized that adding PDS0101 to the treatment of patients receiving checkpoint inhibitors could result in greater clinical benefit.

VERSATILE-002 enrolled patients with relapsed or metastatic HPV16-related HNSCC who were at least 18 years of age and were either naïve or refractory to checkpoint inhibitors and had a composite positive PD-L1 score (CPS) of 1 or greater.2.3 Patients also had to have acceptable organ function, an ECOG performance status of 0 or 1, and recover from any toxicities or complications if they had previously undergone major surgery or exposure to radiation greater than 30 Gy.3

The study used a two-stage Simon design in this population. Patients received pembrolizumab 200 mg intravenously every 3 weeks in combination with PDS0101 for cycles 1 through 4 and 12. Pembrolizumab was continued until disease progression, intolerance, or up to 35 cycles.

At the 2022 ASCO Annual Meeting, investigators reported initial safety and efficacy data from 19 checkpoint inhibitor-naïve patients with a CPS of 1 or greater (n=19), a CPS of 20 or greater (n=7), and an ECOG Power state 0 or 1.

Among 17 patients with available imaging data, the best overall response rate with the doublet was 41.2% (n=7); these included 2 complete responses (CRs) and 5 partial responses (PRs). In addition, 35.3% (n=6) achieved stable disease (SD) and 23.5% (n=4) disease progression. The CR+PR+SD rate with the combination was 76.5% (n=13).

Median progression-free survival (PFS) and overall survival (OS) have not yet been reached in this early cohort. The 9-month PFS rate with the regimen was 55.2% (95% CI, 31.9% – 78.4%) and the 9-month OS rate was 87.2% (95% CI, 70.4% – not evaluable).

A total of 19 patients made up the safety population. The median number of PDS0101 doses received was 4.0 (range 1.0-5.0) and the median duration of treatment was 2.2 months (range 0.0-7.7). The median number of pembrolizumab doses received was 9.0 (range 1.0-18.0) and the median duration of treatment was 5.9 months (range 0.0-11.9). Notably, none of the patients required a dose reduction or discontinuation of either immunotherapeutic agent.

Among checkpoint inhibitor-naïve patients (n=19), 94.7% experienced treatment-emergent adverse events (TEAEs); these effects were grade 1 in 15.8% (n=3) of patients, grade 2 in 42.1% (n=8), grade 3 in 26.3% (n=5), and grade 5 in 10.5 % (n=2). Based on investigator assessment, no grade 3 or greater TEAEs attributed to study treatment were observed, and no serious treatment-emergent TEAEs occurred.

Investigators concluded that Phase 1 of the study was sufficiently successful to warrant progression to Phase 2 in this patient population. In patients who are refractory to checkpoint inhibitors, phase 1 will continue. Further response analyzes on HPV-specific CD8 and CD4 T cells are planned.

Three additional Phase 2 studies are ongoing to further evaluate the PDS0101 combination treatment in patients with advanced HPV-associated cancer (NCT04287868), locally advanced cervical cancer (NCT04580771) and early-stage premetastatic HPV-associated oropharyngeal cancer (NCT05232851). .


  1. PDS Biotechnology receives FDA Fast Track Designation for lead candidate PDS0101. press release. PDS Biotechnology Corporation. June 2, 2022. Accessed June 16, 2022. https://bit.ly/3mSq2WL
  2. Weiss J, Chintakuntlawar A, Price KA, et al. PDS0101, a novel type I interferon and CD8 T-cell activating immunotherapy in combination with pembrolizumab in patients with recurrent/metastatic HPV16-positive head and neck squamous cell carcinoma (HNSCC). J Clin Oncol. 2022;40(Supplement 16):6041. doi:10.1200/JCO.2022.40.16_suppl.6041
  3. Study of the I/O combination of PDS0101 and pembrolizumab in patients with HPV16+ recurrent and/or metastatic HNSCC (VERSATILE002). ClinicalTrials.gov. Updated April 29, 2022. Accessed June 16, 2022. https://clinicaltrials.gov/ct2/show/NCT04260126


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