A Vaccine (PDS0101) Alone or in Combination With Pembrolizumab for the Treatment of Locally Advanced Human Papillomavirus-Associated Oropharynx Cancer

PRIMARY OBJECTIVE:

I. To determine pathologic and human papillomavirus cell-free tumor deoxyribonucleic acid (ctHPVDNA) response to liposomal HPV-16 E6/E7 multipeptide vaccine PDS0101 (PDS0101) or PDS0101 plus pembrolizumab in patients with high risk human papillomavirus-associated oropharynx cancer (HPV-OPSCC).

SECONDARY OBJECTIVES:

I. To determine tumor response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

II. To determine progression-free survival and overall survival.

TERTIARY OBJECTIVES:

I. To determine the safety of PDS0101 delivered alone or with pembrolizumab.

CORRELATIVE RESEARCH OBJECTIVES:

I. Determine the changes in tumor microenvironment (TME) with PDS0101 alone or with pembrolizumab.

II. Determine circulating ctHPVDNA as a biomarker for tumor response. III. Determine HPV16-specific T-cell response utilizing multiplex flow cytometry and other parameters.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive PDS0101 subcutaneously (SC) on day 1 of each cycle. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/CT and blood sample collection throughout the trial. Patients may undergo a biopsy during screening and on the trial.

ARM B: Patients receive PDS0101 SC on day 1 and pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or FDG-PET/CT and blood sample collection throughout the trial. Patients may undergo a biopsy during screening and on the trial.

After completion of study treatment, patients are followed every 3 months for up to 2 years.