A Study of Atezolizumab Plus Tiragolumab and Atezolizumab Plus Placebo as First-Line Treatment in Participants With Recurrent/Metastatic PD-L1 Positive Squamous Cell Carcinoma of the Head and Neck

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the efficacy of atezolizumab plus tiragolumab and atezolizumab plus placebo as first-line (1L) treatment in recurrent/metastatic PD-L1-positive squamous cell carcinoma of the head and neck (SCCHN) on the basis of confirmed objective response rate. In addition, safety, pharmacokinetics, immunogenicity of atezolizumab and tiragolumab will be evaluated.

Official Title
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A Phase II, Randomized, Double Blind Study of Atezolizumab Plus Tiragolumab and Atezolizumab Plus Placebo as First-Line Treatment in Patients With Recurrent/Metastatic PD-L1 Positive Squamous Cell Carcinoma of the Head and Neck

Conditions
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Squamous Cell Carcinoma of Head and Neck

Intervention / Treatment
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* Drug: Atezolizumab
* Drug: Tiragolumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically or cytologically confirmed recurrent/metastatic SCCHN involving the oropharynx, oral cavity, larynx, or hypopharynx, that is considered incurable by local therapies Known results from human papillomavirus (HPV) status test for oropharyngeal carcinoma No prior systemic therapy for metastatic and/or recurrent SCCHN Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Tumor PD-L1 expression as determined by PD-L1 immunohistochemistry assay Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Life expectancy >=12 weeks Key Exclusion Criteria: Disease suitable for local therapy with curative intent Progressive or recurrent disease within 6 months of the last dose of curative intent systemic treatment for locally advanced SCCHN Rapidly progressing disease in the opinion of the treating investigator Grade >=2 unresolved toxicity related to surgery or other prior therapies Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases History of leptomeningeal disease Active or history of autoimmune disease or immune deficiency History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan History of additional malignancy other than SCCHN within 5 years prior to randomization Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-TIGIT, anti-PD-L1, and anti-PD-1 therapeutic antibodies Treatment with systemic immunostimulatory agents or systemic immunosuppressive medication Pregnancy or breastfeeding

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 |
| --- | --- |
| Experimental: Atezolizumab + Tiragolumab<br>Participants will receive atezolizumab followed by tiragolumab every three weeks (Q3W) on Day 1 of each 21-day cycle. | Drug: Atezolizumab<br>* Atezolizumab at a fixed dose of 1200 mg will be administered by intravenous (IV) infusion Q3W on Day 1 of each 21-day cycle.<br>* Other names: Tecentriq; RO5541267;Drug: Tiragolumab<br>* Tiragolumab at a fixed dose of 600 mg will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.<br>* Other names: RO7092284;|
| Placebo Comparator: Atezolizumab + Placebo<br>Participants will receive atezolizumab followed by placebo Q3W on Day 1 of each 21-day cycle. | Drug: Atezolizumab<br>* Atezolizumab at a fixed dose of 1200 mg will be administered by intravenous (IV) infusion Q3W on Day 1 of each 21-day cycle.<br>* Other names: Tecentriq; RO5541267;Drug: Placebo<br>* Placebo will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed Objective Response Rate (ORR) |  | Up to approximately 43 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) |  | Up to approximately 43 months | 
| Progression-Free Survival (PFS) |  | Up to approximately 43 months | 
| Overall Survival (OS) |  | Up to approximately 43 months | 
| Progression-Free Survival Rate at 6 Months |  | Month 6 | 
| Overall Survival Rate at 6 Months and 12 Months |  | Month 6, Month 12 | 
| Time to Confirmed Deterioration (TTCD) in Patient-Reported Physical Functioning |  | Up to approximately 43 months | 
| Percentage of Participants With Adverse Events (AEs) |  | Up to approximately 43 months | 
| Minimum Serum Concentration (Cmin) of Atezolizumab |  | Predose and 30 minutes postdose on Day 1 of Cycle 1 (each cycle is 21 days), predose on Day 1 of Cycles 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit up to approximately 43 months | 
| Maximum Serum Concentration (Cmax) of Atezolizumab |  | Predose and 30 minutes postdose on Day 1 of Cycle 1 (each cycle is 21 days), predose on Day 1 of Cycles 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit up to approximately 43 months | 
| Cmin of Tiragolumab |  | Predose and 30 minutes postdose on Day 1 of Cycle 1 (each cycle is 21 days), predose on Day 1 of Cycles 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit up to approximately 43 months | 
| Cmax of Tiragolumab |  | Predose and 30 minutes postdose on Day 1 of Cycle 1 (each cycle is 21 days), predose on Day 1 of Cycles 2, 3, 4, 8, 12, 16 and at treatment discontinuation visit up to approximately 43 months | 
| Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab |  | From baseline up to approximately 43 months | 
| Number of Participants With ADAs to Tiragolumab |  | From baseline up to approximately 43 months |