FDA Grants Fast Track Status to PDS0101/Pembrolizumab Combo for Recurrent or Metastatic, HPV16+ Head and Neck Cancer

The FDA has granted a fast track designation to PDS0101 for use in combination with pembrolizumab in patients with recurrent or metastatic HPV16-positive head and neck cancer.

The FDA has granted a fast track designation to PDS0101 for use in combination with pembrolizumab (Keytruda) in patients with recurrent or metastatic HPV16-positive head and neck cancer, according to an announcement from PDS Biotechnology Corporation.1

The doublet is currently under investigation in the open-label, multicenter, phase 2 VERSATILE-002 trial (NCT04260126), in which it was shown to have preliminary evidence of clinical activity in most patients with checkpoint inhibitor–naïve, human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC), as well as a favorable toxicity profile.2

“We are thrilled that the FDA granted fast track designation for PDS0101 in combination with [pembrolizumab],” Frank Bedu-Addo, chief executive officer of PDS Biotechnology Corporation, stated in a press release. “The HPV-associated head and neck cancer prevalence continues to rise, leaving this affected group with limited treatment options to date. Receiving this designation underscores the potential of the Versamune® platform and the need for a new therapy that may improve outcomes for this with this devastating disease.”

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

The investigative agent has been found to have antitumor synergy when paired with checkpoint inhibitors. Investigators have hypothesized that the addition of PDS0101 to the treatment of patients who are receiving checkpoint inhibitors may result in a stronger clinical benefit.

VERSATILE-002 enrolled patients with recurrent or metastatic HPV16-related HNSCC who were at least 18 years of age and who were either naïve or refractory to checkpoint inhibitors and who had a PD-L1 combined positive score (CPS) of 1 or higher.2,3 Patients were also required to have acceptable organ function, an ECOG performance status of 0 or 1, and have recovered from any toxicity or complications if they had previously undergone major surgery or radiation of higher than 30 Gy.3

The trial utilized a Simon 2-stage design in this population. Patients received intravenous pembrolizumab at 200 mg every 3 weeks in combination with PDS0101 for cycles 1 through 4 and 12. Pembrolizumab was continued until progressive disease, intolerance, or up to 35 cycles.

At the 2022 ASCO Annual Meeting, investigators reported initial safety and efficacy data on 19 checkpoint inhibitor–naïve patients with a CPS of 1 or higher (n = 19), a CPS of 20 or higher (n = 7), and an ECOG performance status of 0 or 1.

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

The 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 comprised the safety population. The median number of PDS0101 doses received was 4.0 (range, 1.0-5.0), and the median treatment duration 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, no patients required dose reduction or discontinuation with either immunotherapy agent.

Among the checkpoint inhibitor–naïve patients (n = 19), 94.7% experienced treatment-emergent adverse effects (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). No grade 3 or higher TEAEs attributed to study treatment were observed per investigator assessment, and no serious treatment-related TEAEs occurred.

Investigators concluded that stage 1 of the study was sufficiently successful to justify proceeding to stage 2 in this population of patients. Accrual to stage 1 in patients who are refractory to checkpoint inhibitors continues. Additional response analyses pertaining to HPV-specific CD8 and CD4 T cells are planned.

Three additional phase 2 studies are underway to further examine PDS0101 combination treatment in patients with advanced HPV-associated cancers (NCT04287868), locally advanced cervical cancer (NCT04580771), and early-stage, pre-metastatic, HPV-associated oropharyngeal cancer (NCT05232851).


  1. PDS Biotechnology granted FDA fast track designation for lead candidate PDS0101. News 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 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
  3. Study of PDS0101 and pembrolizumab combination I/O in subjects with HPV16+ recurrent and/or metastatic HNSCC (VERSATILE002). ClinicalTrials.gov. Updated April 29, 2022. Accessed June 16, 2022. https://clinicaltrials.gov/ct2/show/NCT04260126