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

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

ArmDescriptionAssigned 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) cisplatin/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) cisplatin/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.

Recruiting Locations

Georgetown U; Lombardi Comp Can
Washington, District of Columbia 20016-1468

More Details

Status
Recruiting
Sponsor
Hoffmann-La Roche

Study Contact

Reference Study ID Number: GO42501 https://forpatients.roche.com/
888-662-6728 (U.S. Only)
global-roche-genentech-trials@gene.com

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.