TMV Vaccine Therapy Alone and With Pembrolizumab for the Treatment of Recurrent and/or Metastatic Head and Neck Squamous Cell Cancer

PRIMARY OBJECTIVE: I. To determine the safety, tolerability, and recommended dose and schedule of TMV vaccine alone or TMV vaccine plus pembrolizumab in patients with surgically resected, recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC). SECONDARY OBJECTIVE: I. To assess vaccine-induce immune activity, antitumor response, progression-free survival (PFS) and overall survival (OS) in adult patients with recurrent and/or metastatic HNSCC administered TMV vaccine alone and TMV vaccine plus pembrolizumab. TERTIARY/EXPLORATORY OBJECTIVES: I. Determine whether TMV vaccine induces immune response and the magnitude of the response. II. Next-generation sequencing (NGS) will be performed using patients' tumor samples and peripheral blood mononuclear cells to assess tumor mutational burden and identify potential neoantigens. OUTLINE: This is a dose-escalation study of TMV vaccine alone and in combination with (fixed-dose) pembrolizumab. Patients are assigned to 1 of 2 cohorts. COHORT 1: Patients provide tissue from standard of care surgery to generate vaccine. The tumor tissue will be banked. When the patient's cancer recurs or metastasis occurs the patient will be treated as indicated. If the cancer progresses, TMV vaccine will be formulated using the banked tumor tissue. Patients receive TMV vaccine intradermally once every 2 weeks for up to 3 doses. Patients undergo echocardiography at baseline and at end of treatment and blood sample collection throughout the study. Patients may also undergo additional computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET) on study. COHORT 2: Patients provide tissue from standard of care surgery to generate vaccine. The tumor tissue will be banked. When the patient's cancer recurs or metastasis occurs the patient will be treated as indicated. If the cancer progresses, TMV vaccine will be formulated using the banked tumor tissue. Patients receive TMV vaccine intradermally once every 2 weeks for up to 3 doses. Patients also receive pembrolizumab intravenously (IV) on day 1 of each cycle. Cycles repeat every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at baseline and at end of treatment and blood sample collection throughout the study. Patients may also undergo additional CT, MRI or PET on study. After completion of study treatment, patients are followed up on day 90 then every 3 weeks for up to 12 months.