A Study Evaluating the Safety and Efficacy of Neoadjuvant and Adjuvant Tiragolumab Plus Atezolizumab, With or Without Platinum-Based Chemotherapy, in Participants With Previously Untreated Locally Advanced Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This study will evaluate the surgical safety and feasibility of atezolizumab plus tiragolumab alone or in combination with platinum-based chemotherapy as neoadjuvant treatment for participants with previously untreated locally advanced non-small cell lung cancer (NSCLC). The study will also evaluate the efficacy, pharmacokinetics, immunogenicity, and safety of atezolizumab plus tiragolumab alone or in combination with platinum-based chemotherapy as neoadjuvant treatment, followed by adjuvant atezolizumab plus tiragolumab or adjuvant platinum-based chemotherapy.

Official Title
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A Phase II, Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Neoadjuvant and Adjuvant Tiragolumab Plus Atezolizumab, With or Without Platinum-Based Chemotherapy, in Patients With Previously Untreated Locally Advanced Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer

Conditions
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Non-Small Cell Lung Cancer (NSCLC)

Intervention / Treatment
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* Drug: Atezolizumab
* Drug: Tiragolumab
* Drug: Carboplatin
* Drug: Cisplatin
* Drug: Pemetrexed
* Drug: Gemcitabine
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Key inclusion criteria: Histologically or cytologically confirmed Stage II, IIIA, or select IIIB (T3N2 only) NSCLC of squamous or non-squamous histology Eligible for R0 resection with curative intent at the time of screening Adequate pulmonary function to be eligible for surgical resection with curative intent Eligible to receive a platinum-based chemotherapy regimen Measurable disease, as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Availability of a representative tumor specimen that is suitable for determination of PD-L1 status Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Normal life expectancy, excluding lung cancer mortality risk Adequate hematologic and end-organ function Negative human immunodeficiency virus (HIV) test at screening Negative serology for active hepatitis B virus (HBV) and active hepatitis C virus (HCV) at screening Key Exclusion Criteria: NSCLC with histology of large cell neuroendocrine carcinoma, sarcomatoid carcinoma, or NSCLC not otherwise specified Small cell lung cancer (SCLC) histology or NSCLC with any component of SCLC Any prior therapy for lung cancer Active or history of autoimmune disease or immune deficiency History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan Active tuberculosis Significant cardiovascular disease NSCLC with an activating EGFR mutation or ALK fusion oncogene Known c-ros oncogene 1 (ROS1) rearrangement History of malignancy other than NSCLC within 5 years prior to screening, with the exception of malignancies with negligible risk of metastasis or death Severe infection within 4 weeks prior to initiation of study treatment or any active infection that, in the opinion of the investigator, could impact patient safety Prior treatment with CD127 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, anti-TIGIT, and anti-PD-L1 therapeutic antibodies Treatment with systemic immunostimulatory agents Treatment with 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A (PD-L1 High)<br>Participants with high programmed death-ligand 1 (PD-L1) expression level will be enrolled in Cohort A and receive neoadjuvant atezolizumab plus tiragolumab for 4 cycles, followed by surgical resection and either adjuvant atezolizumab plus tiragolumab for 16 cycles or adjuvant chemotherapy for 4 cycles at the discretion of the investigator. Chemotherapy may include: cisplatin/carboplatin + pemetrexed (for non-squamous only) cisplatin/carboplatin + gemcitabine (for squamous only) carboplatin + paclitaxel | Drug: Atezolizumab<br>* Atezolizumab 1200 mg will be administered by intravenous (IV) infusion on Day 1 of each 21-day cycle.<br>* Other names: Tecentriq;Drug: Tiragolumab<br>* Tiragolumab 600 mg will be administered by IV infusion on Day 1 of each 21-day cycle.<br>* Other names: MTIG7192A;Drug: Carboplatin<br>* Carboplatin at initial target area under the concentration curve (AUC) of 5 or 6 mg/mL/min will be administered by IV infusion on Day 1 of each 21-day cycle.<br>Drug: Cisplatin<br>* Cisplatin at 75 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.<br>Drug: Pemetrexed<br>* Pemetrexed at 500 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.<br>Drug: Gemcitabine<br>* Gemcitabine at 1000 or 1250 mg/m^2 will be administered by IV infusion on Days 1 and 8 of each 21-day cycle.<br>Drug: Paclitaxel<br>* Paclitaxel at 175 or 200 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.<br>|
| Experimental: Cohort B (PD-L1 All Comers)<br>All comers, which are participants with any PD-L1 expression level, will be enrolled in Cohort B and receive neoadjuvant atezolizumab plus tiragolumab plus chemotherapy for 4 cycles, followed by surgical resection and adjuvant atezolizumab plus tiragolumab for 16 cycles. Chemotherapy may include: cisplatin/carboplatin + pemetrexed (for non-squamous only) cisplatin/carboplatin + gemcitabine (for squamous only) carboplatin + paclitaxel | Drug: Atezolizumab<br>* Atezolizumab 1200 mg will be administered by intravenous (IV) infusion on Day 1 of each 21-day cycle.<br>* Other names: Tecentriq;Drug: Tiragolumab<br>* Tiragolumab 600 mg will be administered by IV infusion on Day 1 of each 21-day cycle.<br>* Other names: MTIG7192A;Drug: Carboplatin<br>* Carboplatin at initial target area under the concentration curve (AUC) of 5 or 6 mg/mL/min will be administered by IV infusion on Day 1 of each 21-day cycle.<br>Drug: Cisplatin<br>* Cisplatin at 75 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.<br>Drug: Pemetrexed<br>* Pemetrexed at 500 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.<br>Drug: Gemcitabine<br>* Gemcitabine at 1000 or 1250 mg/m^2 will be administered by IV infusion on Days 1 and 8 of each 21-day cycle.<br>Drug: Paclitaxel<br>* Paclitaxel at 175 or 200 mg/m^2 will be administered by IV infusion 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 |
| --- | --- | --- |
| Number of Participants With Surgical Delays |  | Up to approximately 6 years | 
| Number of Participants With Operative and Post-operative Complications |  | Up to approximately 6 years | 
| Number of Participants With Surgical Cancellations Related to Study Treatment |  | Up to approximately 6 years | 
| Percentage of Participants With Adverse Events |  | Up to approximately 6 years | 
| Percentage of Participants Who Achieve Major Pathological Response (MPR) |  | At the time of surgery (approximately Weeks 17-20) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Pathological Complete Response (pCR) |  | At the time of surgery (approximately Weeks 17-20) | 
| Event Free Survival (EFS) |  | From baseline to disease progression that precludes surgical resection, or local or distant disease recurrence after surgery, or death from any cause (up to approximately 6 years) | 
| Serum Concentrations of Atezolizumab |  | Day 1 of Cycle 1 (cycle=21 days): pre-dose and 30 minutes (min) post-dose; Day 1 of Cycles 2, 3, 4, 5, 8, 12, 16: pre-dose; at treatment discontinuation (TD) visit (up to approximately 9 months) | 
| Serum Concentrations of Tiragolumab |  | Day 1 of Cycle 1 (cycle=21 days): pre-dose and 30 min post-dose; Day 1 of Cycles 2, 3, 4, 5, 8, 12, 16: pre-dose; at TD visit (up to approximately 9 months) | 
| Percentage of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab |  | Prior to the first infusion on Day 1 of Cycles 1, 2, 3, 4, 5, 8, 12 and 16 (cycle=21 days) and at TD visit (up to approximately 9 months) | 
| Percentage of Participants With ADAs to Tiragolumab |  | Prior to the first infusion on Day 1 of Cycles 1, 2, 3, 4, 5, 8, 12 and 16 (cycle=21 days) and at TD visit (up to approximately 9 months) |