The FDA has provided PDS Biotechnology Corporation with guidance on the required contents of a design for a potential registrational trial examining PDS0101 in combination with PDS0301 and an FDA-approved immune checkpoint inhibitor in patients with recurrent or metastatic human papillomavirus–positive, ICI-refractory head and neck cancer.
A Type B Meeting has been completed and the FDA has provided PDS Biotechnology Corporation with guidance on the required contents of a design for a potential registrational trial examining PDS0101 in combination with PDS0301 and an FDA-approved immune checkpoint inhibitor (ICI) in patients with recurrent or metastatic human papillomavirus (HPV)–positive, ICI-refractory head and neck cancer.1
PDS0101 is a Versamune-based immunotherapy that is designed to trigger a strong targeted T cell attack against HPV-positive cancers.2 Interim data with the agent have indicated that it can produce effective immune responses, and when combined with other approaches, it can provide substantial disease control by shrinking tumors, delaying progressive disease, and/or extending survival.1
An investigational fusion protein of a cancer-targeting antibody and interleukin-12, PDS0301 strengthens the proliferation, potency, and longevity of T cells within the tumor microenvironment. The agent is designed to overcome tumor immune suppression by leveraging a different mechanism than that of checkpoint inhibitors.
“We are pleased with the guidance from the FDA on key elements of a study design to progress the development of our assets PDS0101 and PDS0301, in combination with a commercial immune checkpoint inhibitor,” Frank Bedu-Addo, PhD, chief executive officer of PDS Biotech, stated in a press release.
In a National Cancer Institute (NCI)–led phase 2 trial (NCT04287868), investigators evaluated a triplet regimen comprised of PDS0101, PDS0301, and bintrafusp alfa in patients with advanced HPV-positive cancers, including anal cancer, cervical cancer, head and neck cancer, vaginal cancer, and vulvar cancer.3
Study participants were given bintrafusp alfa at 1200 mg intravenously every 2 weeks plus PDS0301 at 16.8 μg/kg subcutaneously every 4 weeks or 8 μg/kg every 2 weeks, and two 0.5-mL subcutaneous injections of PDS010 every 4 weeks.4 Notably, all participants were refractory to chemotherapy and most (90%) had radiation treatment fail.
Data from an interim analysis of the trial showed that in 29 patients with ICI-refractory disease, the triplet combination resulted in a median overall survival (OS) of 21 months; this was noted to compare favorably with historical data showing a median survival of 3 to 4 months for this population. In those with ICI-naïve disease, the median OS had not yet been reached. The objective response rate (ORR) was 63% in those with ICI-refractory disease who received the optimal dose of the triplet regimen (n = 8), and 88% in those with ICI-naïve disease.
Regarding safety, 48% of 50 evaluable patients reported treatment-related adverse effects (AEs) that were grade 3 or higher in severity; 4% of patients experienced grade 4 toxicities.
“This concurrence to substitute an FDA-approved commercially available ICI for the investigational agent studied in the NCI trial simplifies the regulatory pathway for this triple combination,” Bedu-Addo added.
PDS0101 is also under investigation in combination with pembrolizumab (Keytruda) in patients with ICI-naïve or -refractory HPV16-positive recurrent or metastatic head and neck squamous cell carcinoma as part of the phase 2 VERSATILE-002 trial (NCT04260126).5 Participants received pembrolizumab at 200 mg intravenously every 3 weeks in combination with subcutaneous PDS0101 in cycles 1 to 4 and in cycle 12.
Data from a prespecified interim analysis of the trial were presented at the 2022 ASCO Annual Meeting and showed that the combination induced an ORR of 41.2% in 17 ICI-naïve patients with a combined positive score of at least 1, which met the primary end point of the trial. Among those who responded, the complete response rate was 11.8% and the partial response rate was 29.4%.
At the time of the analysis, median progression-free survival (PFS) was not yet reached, nor was the median OS. The 9-month PFS rate with the combination was 55.2% (95% CI, 31.9%-78.4%), and the 9-month OS rate was 87.2% (95% CI, 70.4%-not evaluable).
Patients were exposed to pembrolizumab for a median of 5.9 months (range, 0.0-11.9) and PDS0101 for a median of 2.2 months (range, 0.0-7.7). No treatment-emergent AEs (TEAEs) were observed, nor any serious treatment-emergent toxicities. TEAEs that were grade 1, 2, or 3 occurred in 15.8%, 42.1%, and 26.3% of patients, respectively.
No participants required dose reductions due to toxicity, and no patients needed to discontinue treatment with either agent.
In June 2022, the FDA granted a fast track designation to PDS0101 plus pembrolizumab for use as a potential therapeutic option in patients with recurrent or metastatic HPV16-positive head and neck cancer.6
“We remain committed to addressing unmet needs in cancer with more effective immunotherapy,” Bedu-Addo added in the press release.