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.~Arm A: Patients receive 2 infusions of atezolizumab intravenously (IV) over 30-60 minutes for up to 15 days prior to definitive surgery and radiation.~Arm A (Adjuvant): Patients received 2 infusions of atezolizumab intravenously (IV) over 30-60 minutes for up to 15 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.
To determine the effect of neoadjuvant atezolizumab alone or in combination with other immune modulating agents on T-cell infiltration in advanced SCCHN. To determine the impact of neo-adjuvant immunotherapy on surgical outcomes.