Preoperative Immunotherapy in Patients With Squamous Cell Carcinoma of the Head and Neck

PRIMARY OBJECTIVES:

I. To determine the effect of neoadjuvant atezolizumab alone or in combination with tiragolumab, tocilizumab, or other immune modulating agent(s) on T-cell infiltration in advanced in advanced squamous cell carcinoma of the head and neck (SCCHN). (Translational).

II. To determine the impact of neo-adjuvant immunotherapy on surgical outcomes. (Clinical).

SECONDARY OBJECTIVES:

I. To describe the changes in T-cell subtypes and other mediators of antitumor immune response induced by neoadjuvant atezolizumab alone or in combination with tiragolumab, tocilizumab, or other immune-modulating agent(s) in advanced SCCHN patients. (Translational).

II. To describe the impact of neoadjuvant, surgical, and adjuvant therapy on peripheral immune responses. (Translational).

III. To establish the safety/toxicity profile of each regimen in the perioperative settings for patients with advanced SCCHN. (Clinical).

EXPLORATORY OBJECTIVES:

I. To characterize changes in the gut microbiome associated with each therapeutic combination.

II. To assess the correlation of disease status with C-Reactive Protein (CRP) and lactate dehydrogenase (LDH) levels.

III. To assess the correlation of disease status with Interleukin 6 (IL-6) levels for participants in Arm C (atezolizumab + tocilizumab).

IV. If leftover tissue and funding are available: To develop immune-competent tumor xenograft models.

V. To determine whether neo-adjuvant immune therapy improves 2-year relapse-free survival (RFS) in patients with SCCHN

OUTLINE: This is a phase II, multi-arm, open-label trial of perioperative atezolizumab alone or in combination with other immune-modulating agents in advanced SCCHN. Based on the results of these initial cohorts, the trial will be amended to explore other novel atezolizumab-based combinations (such as atezolizumab in combination with another immuno-oncology (IO) agent, chemotherapeutics, or a molecularly targeted agent that could potentiate the activity of atezolizumab). Each of these new cohorts will be tested and enrolled to in sequential, non-randomized fashion.