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

Purpose/Objective(s) PDS0101 is a novel, investigational HPV-targeted immunotherapy that stimulates a potent targeted T cell attack against HPV-positive cancers utilizing a mixture of HPV16 E6 and E7 peptides pools delivered subcutaneously with cationic (positively charged) lipid nanoparticles. Initial studies of PDS0101 in combination with pembrolizumab in patients with metastatic HPV16-positive recurrent/metastatic HNSCC demonstrated clinical activity with notable polyfunctional HPV16-specific CD4 and CD8 T cell activation. Limited data exist in the curative intent setting. MC200710 (NCT05232851) is an ongoing prospective window of opportunity study of neoadjuvant PDS0101 with or without pembrolizumab prior to surgery or chemoradiation. Materials/Methods Patients with high risk locally advanced HPV16-postive oropharyngeal carcinoma, defined as multiple or bilateral nodes, radiographic extranodal extension, or lymph nodes >6cm receive two cycles of PDS101 with or without pembrolizumab. The two cycles are given 21 days apart and patients undergo restaging prior to surgical resection. The primary objectives are safety in addition to determining pathologic response and ctDNA response (ctHPVDNA, liquid biopsies). The pathologic response (pTR) is defined as necrosis, keratinous debris, giant cells/histiocytes as percentage of total tumor bed area. Patients will be considered responders with a pTR1 (10-49%) or greater or if they have >= 50% decreased in ctHPVDNA from baseline. Results Eight of a planned 20 eligible patients have been accrued on study. An observed response rate of at least 20% for either pathologic response or ctHPVDNA response will be deemed worthy of further investigation for each arm. Secondary endpoints include radiologic response, progression free survival, and overall survival. Correlative analyses include immunologic query of peripheral blood mononuclear cells (PBMCs) for HPV16-specific immune response over time and in relation to pathologic and ctDNA assessment. Conclusion MC200710 is a trial in progress investigating the pathologic and ctDNA response to two cycles of neoadjuvant PDS0101 with or without pembrolizumab prior to surgery in patients with HPV associated oropharyngeal carcinoma.