A Study of Tiragolumab in Combination With Atezolizumab in Chemotherapy-Naïve Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

A Phase II, Randomized, Blinded, Placebo-Controlled Study of Tiragolumab, An Anti-TIGIT Antibody, In Combination With Atezolizumab In Chemotherapy-Naïve Patients With Locally Advanced Or Metastatic Non-Small Cell Lung Cancer

This study will evaluate the safety and efficacy of tiragolumab plus atezolizumab compared with placebo plus atezolizumab in chemotherapy-naive patients with locally advanced unresectable or metastatic PD-L1-selected non-small cell lung cancer (NSCLC), excluding patients with a sensitizing EGFR mutation or ALK translocation.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Tiragolumab; Drug: Placebo; Drug: Atezolizumab

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Angers, France, 49055
    • ICO Paul Papin
  • Bordeaux, France, 33076
    • Institut Bergonié Centre Régional de Lutte Contre Le Cancer de Bordeaux Et Sud Ouest
  • Dijon, France, 21079
    • Centre Georges Francois Leclerc
  • Marseille, France, 13015
    • Hopital Nord AP-HM
  • Saint-Herblain, France, 44115
    • Institut de Cancérologie de l'Ouest
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia
  • Belgrade, Serbia, 11070
    • Clinical Hospital Center Bezanijska Kosa
  • Južnobanatski Okrug
    • Kamenitz, Južnobanatski Okrug, Serbia, 21204
      • Institute of Lung Diseases Vojvodina
• South Korea
  • Cheongju-si, South Korea, 28644
    • Chungbuk National University Hospital
  • Gyeonggi-do, South Korea, 13620
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 03181
    • Kangbuk Samsung Hospital
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
• Spain
  • Alicante, Spain, 03010
    • Hospital General Universitario de Alicante
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron - PPDS
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta de Hierro - Majadahonda
  • Madrid, Spain, 28036
    • Clinica Universitaria Navarra (Madrid)
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Malaga ? Hospital General
  • Seville, Spain, 41013
    • Hospital Universitario Virgen Del Rocio
  • Seville, Spain, 41013
    • Centro Medico Quironsalud Sagrado Corazon
  • Barcelona
    • Badalona, Barcelona, Spain, 8916
      • Hospital Univ Germans Trias i Pujol
  • LAS Palmas
    • Las Palmas de Gran Canaria, LAS Palmas, Spain, 35016
      • Complejo Hospitalario Universitario Insular?Materno Infantil
• Taiwan
  • New Taipei City, Taiwan, 23561
    • Taipei Medical University ?Shuang Ho Hospital
  • North Dist., Taiwan, 70403
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 1121
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital - Linkou
• United States
  • Arizona
    • Tempe, Arizona, United States, 85284
      • Arizona Oncology Associates, PC - HAL
  • Florida
    • Fort Myers, Florida, United States, 33901
      • SCRI Florida Cancer Specialists South
    • St. Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists - NORTH - SCRI - PPDS
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Illinois Cancer Specialists
    • Peoria, Illinois, United States, 61615
      • Illinois Cancer Care
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • Research Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • SCRI Tennessee Oncology
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, PC
  • Washington
    • Vancouver, Washington, United States, 98684
      • Northwest Cancer Specialists - Vancouver

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• ECOG Performance Status of 0 or 1
• Histologically or cytologically documented locally advanced unresectable NSCLC, recurrent, or metastatic NSCLC of either squamous or non-squamous histology
• No prior systemic treatment for locally advanced unresectable or metastatic NSCLC
• Tumor PD-L1 expression
• Measurable disease, as defined by RECIST v1.1
• Life expectancy >=12 weeks
• Adequate hematologic and end-organ function
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria:

Cancer-Specific Exclusions:

• Patients with NSCLC known to have a sensitizing mutation in the EGFR gene or an ALK fusion oncogene
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
• Spinal cord compression not definitively treated with surgery and/or radiation, and/or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >=2 weeks prior to screening
• History of leptomeningeal disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
• Uncontrolled tumor-related pain
• Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
• Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and/or treated with expected curative outcome

General Medical Exclusions:

• Pregnant and lactating women
• Significant cardiovascular disease
• Severe infections within 4 weeks prior to randomization
• Major surgical procedure other than for diagnosis within 4 weeks prior to randomization

Treatment-Specific Exclusions:

• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins; known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
• History of autoimmune disease
• Prior allogeneic bone marrow transplantation or solid organ transplantation
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• Positive test for human immunodeficiency virus (HIV) and/or active hepatitis B or hepatitis C or active tuberculosis
• Administration of a live, attenuated vaccine within 4 weeks prior to randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo + Atezolizumab; Participants will receive atezolizumab at a fixed dose of 1200 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle and placebo administered by IV infusion Q3W on Day 1 of each 21-day cycle.	Drug: Placebo; Placebo will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.; Drug: Atezolizumab; Atezolizumab at a fixed dose of 1200 mg will be administered first by IV infusion Q3W on Day 1 of each 21-day cycle.; Other Names: Tecentriq
Experimental: Tiragolumab + Atezolizumab; Participants will receive atezolizumab at a fixed dose of 1200 mg administered by intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle and tiragolumab at a dose of 600 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle.	Drug: Tiragolumab; Tiragolumab at a fixed dose of 600 mg will be administered by IV infusion Q3W on Day 1 of each 21-day cycle.; Other Names: MTIG7192A; Drug: Atezolizumab; Atezolizumab at a fixed dose of 1200 mg will be administered first by IV infusion Q3W on Day 1 of each 21-day cycle.; Other Names: Tecentriq

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR was defined as a complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target lesions) must have a reduction in short axis to <10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off.	From baseline until a total of 80 progression-free survival (PFS) events have occurred (up to approximately 11 months)
Progression-free Survival (PFS)	PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline) or unequivocal progression of existing non-target lesions. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm. Kaplan-Meier (KM) methodology was used to estimate the median PFS.	From baseline until a total of 80 PFS events have occurred (up to approximately 11 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Objective Response (DOR)	DOR was defined as the time from the first occurrence of a documented objective response (OR) (CR or PR) to PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. CR was defined as the disappearance of all target and non-target lesions and normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target lesions) must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline) or unequivocal progression of existing non-target lesions. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm. KM methodology was used to estimate the median DOR.	Up to approximately 36 months
Overall Survival (OS)	OS was defined as the time from randomization to death from any cause. KM methodology was used to estimate the median OS.	Up to approximately 36 months
Number of Participants With Adverse Events (AEs)	An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	From initiation of study drug up to approximately 83.7 months
Minimum Serum Concentration (Cmin) of Tiragolumab		Predose on Day 1 of Cycles 1, 3 and 11 (Cycle length = 21 days)
Cmin of Atezolizumab		Predose on Day 1 of Cycles 1, 3 and 11 (Cycle length = 21 days)
Number of Participants With Treatment-Emergent Anti-drug Antibodies (ADAs) to Tiragolumab	Participants who received tiragolumab were considered to be treatment-emergent 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 units (t.u.) greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample has been reported here.	Up to approximately 36 months
Number of Participants With Treatment-Emergent ADAs to Atezolizumab	Participants who received atezolizumab were considered to be treatment-emergent 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 units (t.u.) greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample has been reported here.	Up to approximately 36 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Cho BC, Abreu DR, Hussein M, Cobo M, Patel AJ, Secen N, Lee KH, Massuti B, Hiret S, Yang JCH, Barlesi F, Lee DH, Ares LP, Hsieh RW, Patil NS, Twomey P, Yang X, Meng R, Johnson ML. Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): primary and follow-up analyses of a randomised, double-blind, phase 2 study. Lancet Oncol. 2022 Jun;23(6):781-792. doi: 10.1016/S1470-2045(22)00226-1. Epub 2022 May 13.
• Guan X, Hu R, Choi Y, Srivats S, Nabet BY, Silva J, McGinnis L, Hendricks R, Nutsch K, Banta KL, Duong E, Dunkle A, Chang PS, Han CJ, Mittman S, Molden N, Daggumati P, Connolly W, Johnson M, Abreu DR, Cho BC, Italiano A, Gil-Bazo I, Felip E, Mellman I, Mariathasan S, Shames DS, Meng R, Chiang EY, Johnston RJ, Patil NS. Anti-TIGIT antibody improves PD-L1 blockade through myeloid and Treg cells. Nature. 2024 Mar;627(8004):646-655. doi: 10.1038/s41586-024-07121-9. Epub 2024 Feb 28.

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2018
• Primary Completion (Actual): June 30, 2019
• Study Completion (Actual): November 14, 2025

Study Registration Dates

• First Submitted: April 17, 2018
• First Submitted That Met QC Criteria: June 19, 2018
• First Posted (Actual): June 20, 2018

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 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; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; atezolizumab; Tiragolumab
• Other Study ID Numbers: GO40290; 2018-000280-81 (EudraCT Number); 2023-508083-30-00 (Ctis)

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