A Study of Atezolizumab (Anti-Pd-L1 Antibody) as Adjuvant Therapy After Definitive Local Therapy in Patients With High-Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of atezolizumab compared with placebo as adjuvant therapy after definitive local therapy in patients with high-risk locally advanced squamous cell carcinoma of the head and neck (SCCHN)

Official Title
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A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab (Anti-Pd-L1 Antibody) as Adjuvant Therapy After Definitive Local Therapy in Patients With High-Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Conditions
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Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Intervention / Treatment
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* Drug: Atezolizumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Histologically or cytologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) Human Papilloma Virus (HPV) status Completed definitive local therapy Absence of metastatic disease as documented by radiographic scans Adequate hematologic and end-organ function For patients receiving therapeutic anticoagulation: stable anticoagulant regimen For women of childbearing potential: agreement to remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 5 months after the last dose of study treatment. Women must refrain from donating eggs during this same period. Confirmed response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) to definitive local therapy documented by CT with contrast or MRI with contract to head and neck region done >= 8 weeks after completion of definitive local therapy and within 28 days prior to initiation of study drug. Exclusion Criteria: Patients who have received surgery alone or radiotherapy alone as definitive local therapy Squamous cell carcinoma of the nasopharynx or paranasal sinuses or non-squamous histology Evidence of disease progression or metastatic disease during or following definitive local therapy documented in post-definitive local therapy screening scans Uncontrolled or symptomatic hypercalcemia Active or history of autoimmune disease or immune deficiency Active tuberculosis Significant cardiovascular disease History of malignancy, including prior SCCHN primary tumors within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death Prior allogeneic stem cell or solid organ transplantation Current treatment with anti-viral therapy for Hepatitis B Virus (HBV) Treatment with systemic immunostimulatory agents Treatment with systemic immunosuppressive medication History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the last dose of study treatment Patients who have received a non-FDA or non-EMA approved anti-EGFR agent or any other non-FDA or non-EMA, approved agent as part of definitive local therapy, unless the unapproved agent was given in addition to an approved agent Any systemic therapies after permitted definitive local therapies

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Atezolizumab<br>Participants will receive Atezolizumab for 16 cycles, or up to 1 year (whichever occurs first) | Drug: Atezolizumab<br>* Atezolizumab intravenous infusion will be administered at a fixed dose on Day 1 of each 21-day cycle for 16 cycles.<br>|
| Experimental: Placebo<br>Participants will receive Placebo for 16 cycles, or up to 1 year (whichever occurs first). | Drug: Placebo<br>* Placebo intravenous infusion will be administered a fixed dose on Day 1 of each 21-day cycle for 16 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-assessed Event Free Survival (EFS) |  | Randomization to the first documented disease recurrence, or disease progression (per Response Evaluation Criteria In Solid Tumors (RECIST v1.1)), or death from any cause, whichever occurs first, through the end of study (approximately 65 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) after Randomization |  | Randomization to death from any cause, through the end of study (approximately 99 months) | 
| Independent Review Facility-assessed Event Free Survival (IRF-assessed EFS) |  | Randomization to the first documented disease recurrence, or disease progression (per RECIST v1.1) or death from any cause, whichever occurs first, through the end of study (approximately 65 months) | 
| Change from baseline in physical function and Quality of Life Global Health Status/Quality of Life Scales of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire |  | Baseline to 3 Months and 6 Months | 
| Percentage of Participants with Adverse Events |  | Baseline until up to 90 days after end of treatment (approximately 99 months) | 
| Serum Concentration of Atezolizumab |  | At pre-defined intervals from Cycle 1, Day 1, through end of treatment (approximately 1 year). | 
| Incidence of ADA Response to Atezolizumab |  | At pre-defined intervals from Cycle 1, Day 1, through end of treatment (approximately 1 year). |