1. Revision of EFS definition 2. Interim OS analysis added to previously planned EFS interim analysis, with related changes to sample size determination 3. Sensitivity analyses of EFS added to assess impacts of missing data, new anti-cancer therapy, loss to follow-up, discontinuation

Voluntary Harmonisation Procedure and related changes, including: rationale to support treatment duration (16 cycles or up to 1 year), reduce risk of overlapping toxicities (28 days or 5 half-lives between investigational medicinal products [IMPs]), optional interim analyses removed.

1. Removal of screening pelvis computer tomography (CT) or magnetic resonance imaging (MRI) 2. Addition of chest CT or MRI at every tumor assessment 3. Addition of contrast requirement for CT or MRI of head and neck, as well as chest and abdomen, with specified exceptions

1. Revised timing of surgery for removal of residual disease, initiation of study treatment, and subsequent assessments 2. Additional exclusion criteria: patients who received unapproved anti-estimated glomerular filtration rate (EGFR) agents or unapproved radiotherapy, patients with current second primary SCCHN, patients who received surgery alone or radiotherapy alone 3. Testing of total carbon dioxide permitted in place of bicarbonate 4. Requirement for testing of hepatitis B virus (HBV) surface antibody removed, hepatitis B surface antigen (HBsAg) and total Hepatitis B core antibody (HBcAb) tested instead 5. Additional safety monitoring for special situations including accidental overdose and medication error 6. Voluntary Harmonisation Procedure and further related changes, including clarification of tissue sample submission after randomization

1. Clarification of eligibility assessment involving clinical staging, with tumor staging and nodal staging to be assessed synchronously 2. Restructuring of inclusion criteria pertaining to prior definitive local therapy, confirmed response to prior local therapy, and absence of metastatic disease 3. Inclusion criteria were modified to allow participation of participants who undergo salvage laryngectomy, to require female contraception and abstaining from egg donation 4. Exclusion criteria were modified to exclude HPV negative participants with TX or NX or Tis, HPV positive participants with T0 or NX, participants with squamous cell carcinoma of the paranasal sinus or any carcinoma of non-squamous histology, participants who underwent prior systemic adjuvant therapy 5. Collection of patient reported outcomes (PROs) was modified to allow telephone assessment, the Quality-of-Life-Head and Neck, Module 35 Questionnaire (QLQ-H & N35) was modified to omit additional questions related to swallowing 6. Guidelines for management of AEs related to atezolizumab were revised to include nephritis 7. Clarification on treatment interruption/withholding and resumption

1. Additional approved indications for atezolizumab included in background 2. Systemic immune activation replaced with hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) 3. Atezolizumab risks and AE management guidelines updated to include myositis, HLH, and MAS; to allow longer treatment interruption and resumption of study treatment; to add laboratory testing and cardiac imaging related to myocarditis

1. Investigator-assessed EFS added as primary endpoint 2. IRF-assessed EFS changed to secondary endpoint 3. Efficacy boundaries for the second interim and final OS analyses were modified 4. China extension cohort added to achieve adequate sample size for cohort-specific analysis of efficacy and safety 5. Immunosuppressive therapy removed from prohibited therapy and added to cautionary therapy to allow for use in immune-mediated adverse events 6. Identified risks and adverse events of special interest (AESIs) associated with atezolizumab were updated 7. AE management guidelines for infusion-related reactions, dermatologic reactions, myositis, cytokine release syndrome (CRS), HLH, and MAS were updated. 8. Pregnancy monitoring and investigator notification language was added

1. Alignment with clinical trials regulation guidelines 2. OS changed from co-primary endpoint to key secondary endpoint to be tested if INV-EFS is positive

Investigators-assessed and IRF EFS assessments at 3 and 4-year landmarks added

1. OS assessment at 5-year landmark added, 1-year landmark removed 2. PRO assessments during follow up reduced to decrease participant burden 3. China extension cohort removed 4. Changed study assumptions about expected outcomes for participants with Stage III and IV SCCHN, including EFS and OS 5. COVID-19 benefit-risk assessment added 6. Futility assessment of EFS added 7. Atezolizumab AE management guidelines updated 8. Updated list of preexisting autoimmune disease and immune deficiencies excluding participants from study participation 9. HLH and MAS replaced systemic inflammatory response syndrome on list of atezolizumab-associated AESIs