Primary Objectives:~To determine the major pathological response rate, defined as <10% viable tumor in the resection specimen, after two cycles of neoadjuvant atezolizumab and tiragolumab in patients with newly diagnosed, local-regionally advanced OCSCC that is PD-L1 CPS ≥1. Response at the primary site and in nodal disease will be evaluated.~Secondary Objectives:~To evaluate the safety of two cycles of atezolizumab and tiragolumab in patients with newly diagnosed, local-regionally advanced OCSCC, as measured by the incidence, nature and severity of adverse events with severity measured by CTCAE V5.~To evaluate the overall response rate (ORR) as measured by RECIST1.1 after two cycles of neoadjuvant atezolizumab and tiragolumab, including complete or partial response (CR+PR).~To evaluate the distribution of percent tumor viability in tumor biopsies and resection specimens after two cycles of atezolizumab and tiragolumab.~To estimate the 12, 18 and 24 month progression-free survival (PFS, defined as time from enrollment to date of progression or death) and overall survival (OS, defined as time from enrollment to death) in the study population.~Exploratory Objectives:~To investigate changes in the tumor microenvionment before and after two cycles of atezolizumab and tiragolumab as measured by multispectral immunofluorescence and single-cell sequencing.~To genetically profile OSCC by use of oral rinse and to measure changes in patient-specific somatic mutations by cfDNA before, during and after neoadjuvant immunotherapy.~To assess polyfunctionality in peripheral blood CD4+ and CD8+ T cells after neoadjuvant immunotherapy, radiotherapy and adjuvant immunotherapy.~To evaluate the symptom severity mean (measured by MDASI-HN), and its association with the major pathological response.
To learn if treatment with tiragolumab and atezolizumab before and after standard of care surgery and chemoradiation (radiation therapy with or without cisplatin/carboplatin) can help to control OCSCC that is PD-L1 CPS positive.