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. (Translational). II. To assess the correlation of disease status with C-Reactive Protein (CRP) and lactate dehydrogenase (LDH) levels. (Translational). III. To assess the correlation of disease status with Interleukin 6 (IL-6) levels for participants in Arm C (atezolizumab + tocilizumab). (Translational). IV. If leftover tissue and funding are available: To develop immune-competent tumor xenograft models. (Translational). V. To determine whether neo-adjuvant immune therapy improves 2-year relapse-free survival (RFS) in patients with SCCHN (Clinical). VI. To develop immune-competent tumor xenograft models (If leftover tissue and funding are available). (Translational). OUTLINE: This is a phase II multi-site, open-label prospective clinical trial of neoadjuvant atezolizumab alone and in combination with tiragolumab, tocilizumab, or additional immune-modulating agents in patients with SCCHN. Participants will be enrolled sequentially into each arm. Arm A: Patients receive 2 infusions of atezolizumab intravenously (IV) over 30-60 minutes between 15 - 42 days prior to definitive surgery and radiation, depending on response and per Investigator's discretion. For the first 9 participants in Arm A (atezolizumab monotherapy), atezolizumab will be administered following surgery and radiation or chemoradiation therapies. Arm A (Adjuvant): Patients received 2 infusions of atezolizumab intravenously (IV) over 30-60 minutes between 15 - 42 days prior to definitive surgery and radiation. In addition to neoadjuvant atezolizumab, the first 9 participants in Arm A (atezolizumab monotherapy) received adjuvant atezolizumab beginning 16 weeks after surgery and radiation, or chemoradiation therapy, every 3 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. Adjuvant atezolizumab will only be initiated if radiation-associated adverse events have resolved to grade 2 or better. Arm B: Patients receive atezolizumab IV over 30-60 minutes for up to 2 courses and tiragolumab administered by IV infusion on Cycle 1 Day 1 of neoadjuvant treatment prior to standard surgery. Arm C: Patients receive atezolizumab IV over 30-60 minutes for up to 2 courses and tocilizumab administered by IV infusion on Cycle 1 Day 1 of neoadjuvant treatment prior to standard surgery. Tocilizumab will be administered (prior to atezolizumab administration) as an intravenous infusion Atezolizumab will be administered 2 hours after the conclusion of the tocilizumab infusion. After completion of study treatment, patients are followed up at 30 days post surgery, 3 months, 6 months, 12 months, and at 24 months. The last participant is anticipated to be enrolled no later than July 31, 2026