Head and Neck Cancer Trial Expands to Include Patients Who Failed Checkpoint Inhibitors

Jared Weiss, MD

The phase 2 VERSATILE-002 trial (NCT04260126) of PDS0101 in combination with pembrolizumab (Keytruda) for patients with advanced head and neck cancer has expanded to include those who have progressed on prior treatment with checkpoint inhibitors (CPI), according to a press release from PDS Biotechnology.¹

These patients will be included in an additional arm of the open-label, multicenter study due to the amended protocol. Originally, this trial was only looking at the PDS0101 and pembrolizumab combination as first-line treatment. Now it will investigate in first-line and CPI-refractory patients with human papilloma virus (HPV)–associated head and neck squamous cell carcinoma who have PD-L1 positive recurrent or metastatic disease.

“There is an enormous unmet medical need in [patients with] advanced head and neck cancer who have failed multiple therapies, including chemotherapy, radiation, and checkpoint inhibitor therapy,” Lauren V. Wood, MD, chief medical officer of PDS Biotech. “We believe the combination of PDS0101 and Keytruda has the potential to significantly improve clinical outcomes for these patients who have limited treatment options.”

The protocol was amended to include patients who have received multiple therapies because of the interim data from another phase 2 trial (NCT04287868) investigating PDS0101 plus 2 investigational immunotherapies, M7824 and NHS-IL12. This study showed an objective response rate (ORR) of 63% (5 out of 8 patients) and 30% or more tumor reduction in patients with HPV16-positive cancer who failed treatment with chemotherapy, radiation, and CPIs.

Patients are actively being recruited for treatment to receive the combination instead of standard-of-care chemotherapy. The additional arm for those with CPI-refractory disease will include about 40 patients. The first 21 patients on this arm will be assessed for safety and objective response before the rest of the patients are enrolled.

In both the first-line and CPI-refectory arms, the primary end point is ORR. Objective response will be measured by radiographic tumor response by RECIST 1.1. Secondary end points include progression-free survival, overall survival, and incidence of treatment-related adverse events. Duration of response and anti-HPV16 E6 and E7 immune responses from treatment will be investigated as well.

In VERSATILE-002, patients will receive pembrolizumab as a 200 mg intravenous (IV)infusion plus 2 0.5 mL subcutaneous injections of PDS0101 given on cycles 1, 2, 3, 4, and 12. Pembrolizumab monotherapy will be administered as a 200 mg IV infusion during cycles 5 through 11 and 13 through 35.

Eligible patients are 18 years of age or older and have HPV16-positive recurrent or metastatic head and neck cancer.² These patients will have recovered from any complications of major surgeries or radiation therapy and will have good overall health on exams and blood work. Patients who are pregnant, have central nervous system metastases, HIV infection, or complications from prior anti-cancer treatment will not be enrolled.

The principal investigator of the VERSATILE-002 study is Jared Weiss, MD, an associate professor of medicine, Division of Oncology, at the University of North Carolina at Chapel Hill School of Medicine and Lineberger Comprehensive Cancer Center.

_References:

_{1. PDS Biotechnology expands VERSATILE-002 study of PDS0101 and Keytruda in advanced head and neck cancer to include patients who have failed prior treatment with checkpoint inhibitors. News release. PDS Biotech. Published June 3, 2021. Accessed June 3, 2021. https://bit.ly/3g5DByh}

_{2. VERSATILE-002. PDS Biotech. Accessed June 3, 2021. https://bit.ly/3uOoazS}