A Study of Tiragolumab in Combination With Atezolizumab in Chemotherapy-Naïve Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Non-small Cell Lung Cancer

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


Participation Criteria
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Eligibility Criteria
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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: Pregnant and lactating women Significant cardiovascular disease Severe infections within 4 weeks prior to randomization Major surgical procedure other than for diagnosis within 4 weeks prior to randomization Treatment-Specific Exclusions: History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins; known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation History of autoimmune disease Prior allogeneic bone marrow transplantation or solid organ transplantation History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan Positive test for human immunodeficiency virus (HIV) and/or active hepatitis B or hepatitis C or active tuberculosis Administration of a live, attenuated vaccine within 4 weeks prior to randomization

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo + Atezolizumab<br>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. | Drug: Atezolizumab<br>* Atezolizumab at a fixed dose of 1200 mg will be administered first by IV infusion Q3W on Day 1 of each 21-day cycle.<br>* Other names: Tecentriq;Drug: Placebo<br>* Placebo will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.<br>|
| Experimental: Tiragolumab + Atezolizumab<br>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. | Drug: Atezolizumab<br>* Atezolizumab at a fixed dose of 1200 mg will be administered first by IV infusion Q3W on Day 1 of each 21-day cycle.<br>* Other names: Tecentriq;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: MTIG7192A;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | 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. | From baseline until a total of 80 progression free survival (PFS) events have occurred (up to approximately 11 months) | 
| Progression Free Survival (PFS) | 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). | From baseline until a total of 80 PFS events have occurred (up to approximately 11 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Objective Response (DOR) | DOR, defined as the time from the first occurrence of a documented objective response (CR or PR) to disease progression (PD), as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. 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. 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). | Up to 6 years | 
| Overall Survival (OS) | OS, defined as the time from randomization to death from any cause. | Up to 6 years | 
| Percentage of Participants With Adverse Events | An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. | 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) | 
| 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) |