A Phase II, Randomized, Blinded, Placebo-Controlled Study of Tiragolumab, An Anti-TIGIT Antibody, In Combination With Atezolizumab In Chemotherapy-Naïve Patients With Locally Advanced Or Metastatic Non-Small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- Atezolizumab
- Conditions
- Non-small Cell Lung Cancer
- Sponsor
- Genentech, Inc.
- Enrollment
- 135
- Locations
- 37
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Completed
- Last Updated
- 3 months ago
Overview
Brief Summary
This study will evaluate the safety and efficacy of tiragolumab plus atezolizumab compared with placebo plus atezolizumab in chemotherapy-naive patients with locally advanced unresectable or metastatic PD-L1-selected non-small cell lung cancer (NSCLC), excluding patients with a sensitizing EGFR mutation or ALK translocation.
Investigators
Eligibility Criteria
Inclusion Criteria
- •ECOG Performance Status of 0 or 1
- •Histologically or cytologically documented locally advanced unresectable NSCLC, recurrent, or metastatic NSCLC of either squamous or non-squamous histology
- •No prior systemic treatment for locally advanced unresectable or metastatic NSCLC
- •Tumor PD-L1 expression
- •Measurable disease, as defined by RECIST v1.1
- •Life expectancy \>=12 weeks
- •Adequate hematologic and end-organ function
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs
- •For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm
Exclusion Criteria
- •Cancer-Specific Exclusions:
- •Patients with NSCLC known to have a sensitizing mutation in the EGFR gene or an ALK fusion oncogene
- •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- •Spinal cord compression not definitively treated with surgery and/or radiation, and/or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for \>=2 weeks prior to screening
- •History of leptomeningeal disease
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- •Uncontrolled tumor-related pain
- •Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
- •Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and/or treated with expected curative outcome
- •General Medical Exclusions:
Arms & Interventions
Placebo + Atezolizumab
Participants will receive atezolizumab at a fixed dose of 1200 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle and placebo administered by IV infusion Q3W on Day 1 of each 21-day cycle.
Intervention: Atezolizumab
Placebo + Atezolizumab
Participants will receive atezolizumab at a fixed dose of 1200 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle and placebo administered by IV infusion Q3W on Day 1 of each 21-day cycle.
Intervention: Placebo
Tiragolumab + Atezolizumab
Participants will receive atezolizumab at a fixed dose of 1200 mg administered by intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle and tiragolumab at a dose of 600 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle.
Intervention: Atezolizumab
Tiragolumab + Atezolizumab
Participants will receive atezolizumab at a fixed dose of 1200 mg administered by intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle and tiragolumab at a dose of 600 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle.
Intervention: Tiragolumab
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
Time Frame: From baseline until a total of 80 PFS events have occurred (up to approximately 11 months)
PFS, defined as the time from randomization to the first occurrence of disease progression (PD), as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline).
Objective Response Rate (ORR)
Time Frame: From baseline until a total of 80 progression free survival (PFS) events have occurred (up to approximately 11 months)
ORR, defined as a complete response (CR) or partial response (PR) on two consecutive occasions \>/=4 weeks apart, as determined by the investigator according to RECIST v1.1. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.
Secondary Outcomes
- Percentage of Participants With Adverse Events(Up to 6 years)
- Duration of Objective Response (DOR)(Up to 6 years)
- Serum Concentrations of Tiragolumab(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days))
- Serum Concentrations of Atezolizumab(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days))
- Overall Survival (OS)(Up to 6 years)
- Percentage of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs)(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 12 Day 1 (each cycle is 21 days))