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

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

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.

Study Overview

• Status: Terminated
• Conditions: Non-Small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: Atezolizumab; Drug: Tiragolumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Gemcitabine; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Sunshine Coast University Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter Maccallum Cancer Institute
• South Korea
  • Gyeonggi-do, South Korea, 16247
    • St. Vincent's Hospital
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
• Spain
  • A Coruña, Spain, 15006
    • Complejo Hospitalario Universitario A Coruña (CHUAC)
  • Barcelona, Spain, 08035
    • Vall d?Hebron Institute of Oncology (VHIO), Barcelona
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
      • ICO L'Hospitalet
    • Sabadell, Barcelona, Spain, 08208
      • Corporacio Sanitaria Parc Tauli
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro
• Switzerland
  • Baden, Switzerland, 5404
    • Kantonsspital Baden
  • Chur, Switzerland, 7000
    • Kantonsspital Graubünden Medizin Onkologie
  • Sankt Gallen, Switzerland, 9007
    • Kantonsspital St. Gallen
  • Winterthur, Switzerland, 8401
    • Kantonsspital Winterthur
  • Zurich, Switzerland, 8091
    • Universitatsspital Zurich
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Cancer Center
    • Los Angeles, California, United States, 90033
      • University of Southern California
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Mineola, New York, United States, 11501
      • Winthrop Univ Hospital
    • New York, New York, United States, 10032-3725
      • Columbia University
    • New York, New York, United States, 10016
      • NYU Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Surgical Delays	Participants were scheduled to undergo surgical resection of their tumor upon completion of four cycles of neo-adjuvant therapy. Prior to the surgery, the attending surgeon and medical oncologist assessed the participant to check if it was clinically feasible for them to undergo surgery (pre-surgical assessment). Surgery was to be done within 30 days of the pre-surgical assessment visit. Assessment of surgical delays were made by assessing the data entered in the electronic case report forms (eCRFs).	Up to approximately 4.7 months
Number of Participants With Operative and Post-operative Complications	Participants who underwent surgical resection of their tumor and had intraoperative or post-operative complications were reported.	From day of surgery up to end of safety follow-up (up to approximately 17.5 months)
Number of Participants With Surgical Cancellations Related to Study Treatment	Participants were scheduled to undergo surgical resection of their tumor upon completion of four cycles of neo-adjuvant therapy. Prior to the surgery, the attending surgeon and medical oncologist assessed the participant for to check if it was clinically feasible for them to undergo surgery (pre-surgical assessment). Surgery was to be done within 30 days of the pre-surgical assessment visit. Assessment of surgical delays were made by assessing the data entered in the eCRFs.	Up to approximately 4.7 months
Number of Participants With Adverse Events (AEs)	AE=any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any of the following: Any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product; Any new disease or exacerbation of an existing disease; Recurrence of an intermittent medical condition not present at baseline; Any deterioration in a laboratory value or other clinical test that is associated with symptoms or leads to a change in study treatment or concomitant treatment or discontinuation from study treatment; AEs that are related to a protocol-mandated intervention, including those that occur prior to assignment of study treatment.	From signing of informed consent to up to 90 days after the final dose of study treatment (Up to approximately 1.7 years)
Major Pathological Response (MPR) Rate	MPR rate was defined as the percentage of participants who achieved MPR. MPR was defined as ≤10% residual viable tumor at the time of surgical resection in the primary tumor, as assessed by the local pathology laboratory. Patients who did not proceed to surgery were considered as non-responders for MPR. 95% confidence interval (CI) was calculated using the Wilson Score Method. Percentages have been rounded off.	At the time of surgical resection (From Day 114 to Day 144)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Pathological Complete Response (pCR)	pCR was defined as the absence of any viable tumor cells in both the primary tumor and all sampled lymph nodes at the time of surgical resection, as assessed by local pathology laboratory. 95% CI was calculated using the Wilson Score Method. Percentages have been rounded off.	At the time of surgical resection (From Day 114 to Day 144)
Event-free Survival (EFS)	EFS was defined as the time from first dose of the study drug to any of the following events, whichever occurs first: disease progression that precludes surgery, as assessed by the investigator; local or distant disease recurrence (including occurrence of new primary NSCLC); or death from any cause. Median was estimated using Kaplan-Meier (K-M) method. 95% CI for median was computed using the method of Brookmeyer and Crowley.	Up to approximately 3.8 years
Serum Concentrations of Atezolizumab at Specified Timepoints		Prior to the first infusion on Day 1 of Cycles 1, 2, 3, 4, 5, 8, 12, and 16; 30 minutes (min) post-infusion Day 1 of Cycle 1; (Cycle=21 days)
Serum Concentrations of Tiragolumab at Specified Timepoints		Prior to the first infusion on Day 1 of Cycles 1, 2, 3, 4, 5, 8, 12, 16; 30 minutes (min) post-infusion Cycle 1 Day 1; (Cycle=21 days)
Percentage of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab	Participants were considered to be ADA positive if they were ADA negative or had missing data at baseline but developed an ADA response following atezolizumab exposure (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (treatment-enhanced ADA response). Percentages have been rounded off.	Up to approximately 3.8 years
Percentage of Participants With ADAs to Tiragolumab	Participants were considered to be ADA positive if they were ADA negative or had missing data at baseline but developed an ADA response following tiragolumab exposure (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (treatment-enhanced ADA response). Percentages have been rounded off.	Up to approximately 3.8 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2021
• Primary Completion (Actual): March 5, 2025
• Study Completion (Actual): March 5, 2025

Study Registration Dates

• First Submitted: April 2, 2021
• First Submitted That Met QC Criteria: April 2, 2021
• First Posted (Actual): April 6, 2021

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Platinum Compounds; Pemetrexed; Gemcitabine; Carboplatin; Paclitaxel; Cisplatin; atezolizumab; Tiragolumab
• Other Study ID Numbers: GO42501; 2020-002853-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No