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: Active, not recruiting
• 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 Contact: Name: Reference Study ID Number: GO42501 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. Only); Email: global-roche-genentech-trials@gene.com

Study Locations

• Australia
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Sunshine Coast University Hospital; The Adem Crosby Centre
  • Victoria
    • Malvern, Victoria, Australia, 3144
      • Cabrini Hospital Malvern
    • Melbourne, Victoria, Australia, 3000
      • PETER MACCALLUM CANCER INSTITUTE; MEDICAL ONCOLOGY; Parkville Cancer Clinical Trials Unit
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of, 16247
    • St. Vincent's Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
• Spain
  • Barcelona, Spain, 08035
    • Vall d?Hebron Institute of Oncology (VHIO), Barcelona
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre; Servicio de Oncologia
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
      • ICO L'Hospitalet; Servicio de oncologia medica
    • Sabadell, Barcelona, Spain, 8208
      • Corporacio Sanitaria Parc Tauli; Servicio de Oncologia
  • LA Coruña
    • A Coruña, LA Coruña, Spain, 15006
      • Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro; Servicio de Oncologia
• Switzerland
  • Baden, Switzerland, 5404
    • Kantonsspital Baden; Medizinische Klinik, Onkologie
  • Chur, Switzerland, 7000
    • Kantonsspital Graubünden Medizin Onkologie; Onkologie und Hämatologie
  • St. Gallen, Switzerland, 9007
    • Kantonsspital St. Gallen; Onkologie/Hämatologie
  • Winterthur, Switzerland, 8401
    • Kantonsspital Winterthur; Medizinische Onkologie
  • Zürich, Switzerland, 8091
    • UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Cancer Center; Division of Medical Oncology & Experimental Therapeutics
    • Irvine, California, United States, 92618
      • City of Hope at Irvine Lennar
    • Los Angeles, California, United States, 90033
      • University of Southern California
  • District of Columbia
    • Washington, District of Columbia, United States, 20016-1468
      • Georgetown U; Lombardi Comp Can
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine; Medical Oncology
  • 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	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	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)

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 (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2028

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): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Folic Acid Antagonists; Carboplatin; Paclitaxel; Pemetrexed; Atezolizumab; Gemcitabine
• 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: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

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