Phase II Trial of Neoadjuvant Chemotherapy (NAC) Alone or in Combination With Immunotherapy Vaccine PRGN-2009 in Subjects With Newly Diagnosed HPV-Associated Oropharyngeal (Head and Neck) Cancer

Background:

• Human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is among the most common HPV-associated malignancies and the incidence is increasing. The prognosis is favorable with >80% 5-year recurrence free survival observed following standard anti-cancer treatments that consist of surgery followed by adjuvant post-operative radiation therapy (PORT) or concurrent chemoradiation (CRT).
• Although oncologic control is excellent, these standard-of-care treatments often lead to radiation-associated long-term toxicity that includes tissue fibrosis resulting in long-term swallow dysfunction and poor quality of life (QOL).
• Neoadjuvant chemotherapy (NAC) followed by surgery has decades of real-world data, with clinical-to-pathologic downstaging or pathologic complete response (pCR) being observed in most patients, >90% 5-year survival, and complete avoidance of radiation treatment in >95% of patients.
• The rate of pCR, clinical-to-pathologic downstaging, and functional outcomes after NAC followed by surgery have not been studied in a formal, prospective clinical study.
• A pilot correlative study of NAC with docetaxel and cisplatin (DC) in patients with newly diagnosed HPV-associated OPSCC conducted at the NIH revealed induction of HPV-specific T cell immunity that associates with clinical outcome (18DC0051).
• PRGN-2009 is a gorilla adenoviral therapeutic vaccine designed to enhance HPV 16/18- specific T-cell responses. The safety and efficacy of PRGN-2009 in patients with newly diagnosed HPV-associated OPSCC have been studied at the NIH Clinical Center (NCT04432597).
• Pre-clinical data indicate that chemotherapy can remodel the tumor microenvironment and enhance immunotherapy, suggesting that the combination of DC and PRGN-2009 may enhance anti-tumor immunity and the rate of pCR beyond that observed with DC alone.

Objective:

-To determine the rate of pCR with NAC (DC) alone or in combination with PRGN-2009 (DCP) in participants with newly diagnosed HPV-associated OPSCC.

Eligibility criteria:

• Pathologically confirmed newly diagnosed surgically resectable stage I or II HPV-positive oropharyngeal squamous cell carcinoma.
• Age >= 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status <= 2 and adequate organ function.

Design:

• Participants diagnosed in the community with newly diagnosed HPV-associated OPSCC will be referred to the NIH Clinical Center for neoadjuvant treatment.
• Participants will be randomized to receive either DC (Arm 1) or DCP (Arm 2) in the neoadjuvant setting. DC is three cycles of intravenous cisplatin plus docetaxel, administered every 21 days. PRGN-2009 is 4 doses of subcutaneous vaccination administered on Day -7 of Cycle 1, and Day 11 of Cycles 1, 2, and 3. Participants will be stratified at registration for stage (I or II).
• Participants will undergo pre- and post-treatment Positron Emission Tomography (PET) / Computed Tomography (CT) and measurement of circulating cell-free HPV DNA.
• Participants will return to the community to receive standard-of-care surgery. The need for pathology-indicated, risk-stratified PORT will be determined per standard of care.
• Pathologic responses and follow-up to assess swallow function, QOL, hearing function, and recurrence-free survival will take place at the NIH Clinical Center.