A Study of Tiragolumab Plus Atezolizumab and Atezolizumab Monotherapy in Participants With Metastatic and/or Recurrent PD-L1-Positive Cervical Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of tiragolumab in combination with atezolizumab and atezolizumab monotherapy in patients with programmed death-ligand 1 (PD-L1)-positive cervical cancer (metastatic and/or recurrent).

Official Title
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A Phase II, Safety, and Efficacy Study of Tiragolumab Plus Atezolizumab and Atezolizumab Monotherapy in Patients With Metastatic and/or Recurrent PD-L1-Positive Cervical Cancer

Conditions
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Cervical Cancer

Intervention / Treatment
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* Drug: Tiragolumab
* Drug: Atezolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix after progression on or after 1-2 lines of prior systemic chemotherapy in the metastatic/recurrent setting that is not amenable to curative treatment with systemic chemotherapy, surgery, and/or radiotherapy Radiologically-measurable disease Eastern Cooperative Oncology Group (ECOG) performance Status of 0 or 1 Cervical cancer tissue for study analysis (archival or fresh biopsy specimen) Life expectancy of at least 12 weeks Adequate hematologic and organ function Female of childbearing potential must be willing to comply with adequate contraception Exclusion Criteria: Treatment with investigational therapy with therapeutic intent within 28 days prior to randomization Active or untreated central nervous system (CNS) or brain metastases Active or history of autoimmune disease or immune deficiency Active tuberculosis Known, clinically significant liver disease Severe infection per investigator judgement at the time of randomization or any active infection that, in the opinion of the investigator, could impact patient safety Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-CTLA-4, anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to randomization Treatment with systemic immunosuppressive medications within 1 week prior to randomization or anticipation of need for systemic immunosuppressive medication during study Pregnant or breastfeeding woman Known hypersensitivity to any component of the tiragolumab or atezolizumab formulations

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tiragolumab plus Atezolizumab<br>Participants will receive tiragolumab and atezolizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. | Drug: Tiragolumab<br>* Tiragolumab at a fixed dose of 600 milligrams (mg) will be administered by intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.<br>* Other names: RO7092284;Drug: Atezolizumab<br>* Atezolizumab at a fixed dose of 1200 mg will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.<br>* Other names: Tecentriq;|
| Experimental: Atezolizumab<br>Participants will receive atezolizumab monotherapy until unacceptable toxicity or loss of clinical benefit as determined by the investigator. | Drug: Atezolizumab<br>* Atezolizumab at a fixed dose of 1200 mg will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.<br>* Other names: Tecentriq;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Independent Review Committee (IRC)-Assessed Objective Response Rate (ORR) |  | From randomization up to approximately 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events |  | Up to 36 months | 
| IRC-Assessed Duration of Response (DOR) |  | First occurrence of a documented objective response to the date of disease progression or death from any cause, whichever occurs first (up to approximately 36 months) | 
| IRC-Assessed Disease Control Rate (DCR) |  | From randomization up to approximately 36 months | 
| Investigator-Assessed Best Clinical Response (BCR) Rate |  | From randomization up to approximately 36 months | 
| Investigator-Assessed DOR |  | First occurrence of a documented objective response to the date of disease progression or death from any cause, whichever occurs first (up to approximately 36 months) | 
| IRC-Assessed Progression-Free Survival (PFS) |  | From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 36 months) | 
| IRC-Assessed PFS Rate at 6 Months |  | At 6 months post-randomization | 
| Overall Survival (OS) |  | From randomization to death from any cause (up to 36 months) | 
| OS Rate at 6 Months and 12 Months |  | At 6 and 12 months post-randomization | 
| Minimum Serum Concentration (Cmin) of Tiragolumab |  | Predose and 30 minutes postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 and at treatment discontinuation (TD) visit (up to 36 months) | 
| Maximum Serum Concentration (Cmax) of Tiragolumab |  | Predose and 30 minutes postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 and at TD visit (up to 36 months) | 
| Cmin of Atezolizumab |  | Predose and 30 minutes postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 and at TD visit (up to 36 months) | 
| Cmax of Atezolizumab |  | Predose and 30 minutes postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 and at TD visit (up to 36 months) | 
| Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab |  | Predose on Day 1 of Cycles 1, 2, 3, 4, 8, 12 and 16 (each cycle is 21 days) and at TD visit (up to 36 months) | 
| Percentage of Participants With ADAs to Atezolizumab |  | Predose on Day 1 of Cycles 1, 2, 3, 4, 8, 12 and 16 (each cycle is 21 days) and at TD visit (up to 36 months) |