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

Roche

Status and phase: Completed; Phase 2

Conditions: Non-Small Cell Lung Cancer (NSCLC)

Treatments: Drug: Tiragolumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Gemcitabine; Drug: Atezolizumab; Drug: Pemetrexed; Drug: Paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT04832854

2020-002853-11 (EudraCT Number)

GO42501

Details and patient eligibility

About

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.

Enrollment: 50 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

Cohort A (PD-L1 High)

Experimental group

Description:

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

Treatment:

Drug: Paclitaxel

Drug: Pemetrexed

Drug: Gemcitabine

Drug: Atezolizumab

Drug: Cisplatin

Drug: Carboplatin

Drug: Tiragolumab

Cohort B (PD-L1 All Comers)

Experimental group

Description:

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

Treatment:

Drug: Paclitaxel

Drug: Pemetrexed

Drug: Gemcitabine

Drug: Atezolizumab

Drug: Cisplatin

Drug: Carboplatin

Drug: Tiragolumab