We Partner 4 Research

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

Purpose

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.

Condition

Non-Small Cell Lung Cancer (NSCLC)

Eligibility

Eligible Ages: Over 18 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

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

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

Study Design

Phase: Phase 2
Study Type: Interventional
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Cohort A (PD-L1 High)	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) carboplatin + gemcitabine (for squamous only) carboplatin + paclitaxel	Drug: Atezolizumab Atezolizumab 1200 mg will be administered by intravenous (IV) infusion on Day 1 of each 21-day cycle. Other names: Tecentriq Drug: Tiragolumab Tiragolumab 600 mg will be administered by IV infusion on Day 1 of each 21-day cycle. Other names: MTIG7192A Drug: Carboplatin 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. Drug: Cisplatin Cisplatin at 75 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle. Drug: Pemetrexed Pemetrexed at 500 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle. Drug: Gemcitabine Gemcitabine at 1000 or 1250 mg/m^2 will be administered by IV infusion on Days 1 and 8 of each 21-day cycle. Drug: Paclitaxel Paclitaxel at 175 or 200 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.
Experimental Cohort B (PD-L1 All Comers)	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) carboplatin + gemcitabine (for squamous only) carboplatin + paclitaxel	Drug: Atezolizumab Atezolizumab 1200 mg will be administered by intravenous (IV) infusion on Day 1 of each 21-day cycle. Other names: Tecentriq Drug: Tiragolumab Tiragolumab 600 mg will be administered by IV infusion on Day 1 of each 21-day cycle. Other names: MTIG7192A Drug: Carboplatin 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. Drug: Cisplatin Cisplatin at 75 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle. Drug: Pemetrexed Pemetrexed at 500 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle. Drug: Gemcitabine Gemcitabine at 1000 or 1250 mg/m^2 will be administered by IV infusion on Days 1 and 8 of each 21-day cycle. Drug: Paclitaxel Paclitaxel at 175 or 200 mg/m^2 will be administered by IV infusion on Day 1 of each 21-day cycle.

More Details

Status: Active, not recruiting
Sponsor: Hoffmann-La Roche

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.