A Study of Tiragolumab in Combination With Atezolizumab Plus Pemetrexed and Carboplatin/Cisplatin Versus Pembrolizumab Plus Pemetrexed and Carboplatin/Cisplatin in Participants With Previously Untreated Advanced Non-Squamous Non-Small Cell Lung Cancer

NCT04619797 | Completed Phase 2 DMC FDA Drug

• 3 other identifiers: BO425922020-002851-392022-502031-20-00
• Study Type: interventional
• Target: 542
• Locations: 21 countries
• Sites: 128

Brief Summary

The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of tiragolumab in combination with atezolizumab plus pemetrexed and carboplatin/cisplatin (Arm A) compared with placebo in combination with pembrolizumab plus pemetrexed and carboplatin/cisplatin (Arm B) in participants with previously untreated, locally advanced unresectable or metastatic non-squamous non-small cell lung cancer (NSCLC). Eligible participants will be randomized in a 1:1 ratio to receive one of the following treatment regimens during the induction phase:

• Arm A: Tiragolumab plus atezolizumab plus pemetrexed and carboplatin or cisplatin
• Arm B: Placebo plus pembrolizumab plus pemetrexed and carboplatin or cisplatin Following the induction phase, participants will continue maintenance therapy with either tiragolumab in combination with atezolizumab and pemetrexed (Arm A) or placebo in combination with pembrolizumab and pemetrexed (Arm B).

Conditions

Non-small Cell Lung Cancer (NSCLC)

Outcome Measures

Primary Outcomes (3)

• Investigator-Assessed Confirmed Objective Response Rate (ORR) (Phase 2)

  Up to approximately 5 years

• Investigator-Assessed Progression-Free Survival (PFS) (Phase 2 and Phase 3)

  From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 5 years)

• Overall Survival (Phase 3)

  From randomization to death from any cause (up to approximately 5 years)

Secondary Outcomes (16)

• Overall Survival (Phase 2)

  From randomization to death from any cause (up to approximately 5 years)

• PFS as Determined by an Independent Review Facility (IRF) (Phase 3)

  From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 5 years)

• Investigator-assessed PFS in Participants With PD-L1 Expression at TC ≥50% and TC ≥1% Cut-off, as Determined by Central Testing With Ventana PD-L1 (SP263) Assay (Phase 3)

  From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 5 years)

• OS in Participants With PD-L1 Expression at TC ≥50% and TC ≥1% Cut-off, as Determined by Central Testing With Ventana PD-L1 (SP263) Assay (Phase 3)

  From randomization to death from any cause (up to approximately 5 years)

• Investigator-Assessed PFS at 6 Months and 12 Months (Phase 3)

  6 months, 12 months

Study Arms (2)

Tiragolumab+Atezolizumab+Pemetrexed+Carboplatin or Cisplatin

EXPERIMENTAL

Induction treatment with tiragolumab in combination with atezolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with tiragolumab in combination with atezolizumab and pemetrexed on Day 1 of each 21-day cycle.

Drug: Tiragolumab; Drug: Atezolizumab; Drug: Pemetrexed; Drug: Carboplatin; Drug: Cisplatin

Placebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin

PLACEBO COMPARATOR

Induction treatment with placebo in combination with pembrolizumab plus pemetrexed and cisplatin or carboplatin will be administered to participants on Day 1 of each 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with placebo in combination with pembrolizumab and pemetrexed on Day 1 of each 21-day cycle.

Drug: Pemetrexed; Drug: Carboplatin; Drug: Cisplatin; Drug: Tiragolumab Matching Placebo; Drug: Pembrolizumab

Interventions

Tiragolumab DRUG

Tiragolumab at a fixed dose of 600 milligrams (mg), administered by intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21-day cycle.

Also known as: MTIG7192A

Tiragolumab+Atezolizumab+Pemetrexed+Carboplatin or Cisplatin

Atezolizumab DRUG

Atezolizumab at a fixed dose of 1200 mg, administered by IV infusion, Q3W on Day 1 of each 21-day cycle.

Also known as: Tecentriq

Tiragolumab+Atezolizumab+Pemetrexed+Carboplatin or Cisplatin

Pemetrexed DRUG

Pemetrexed 500 milligrams per square meter (mg/m\^2), administered by IV infusion, Q3W on Day 1 of each 21-day cycle.

Placebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin; Tiragolumab+Atezolizumab+Pemetrexed+Carboplatin or Cisplatin

Carboplatin DRUG

Carboplatin at dose of area under the concentration-time curve (AUC) of 5, administered by IV infusion, Q3W on Day 1 of each 21-day cycle for 4 cycles.

Placebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin; Tiragolumab+Atezolizumab+Pemetrexed+Carboplatin or Cisplatin

Cisplatin DRUG

Cisplatin 75 mg/m\^2, administered by IV infusion, Q3W on Day 1 of each 21-day cycle for 4 cycles.

Placebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin; Tiragolumab+Atezolizumab+Pemetrexed+Carboplatin or Cisplatin

Tiragolumab Matching Placebo DRUG

Matching placebo, administered by IV infusion, Q3W on Day 1 of each 21-day cycle.

Placebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin

Pembrolizumab DRUG

Pembrolizumab at a fixed dose of 200 mg, administered by IV infusion, Q3W, on Day 1 of each 21-day cycle.

Placebo+Pembrolizumab+Pemetrexed+Carboplatin or Cisplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Histologically or cytologically documented locally advanced unresectable or metastatic non-squamous NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy
• No prior systemic treatment for metastatic non-squamous NSCLC
• Known tumor programmed death-ligand 1 (PD-L1) status
• Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
• Life expectancy \>= 12 weeks
• Adequate hematologic and end-organ function
• Negative human immunodeficiency virus (HIV) test at screening
• Serology test negative for active hepatitis B virus or active hepatitis C virus at screening.

You may not qualify if:

• Mutations in epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) fusion oncogene
• Pulmonary lymphoepithelioma-like carcinoma subtype of NSCLC
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
• Active or history of autoimmune disease or immune deficiency
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
• History of malignancy other than NSCLC within 5 years prior to randomization, with the exception of malignancies with a 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
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated protein 4, anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment
• Known allergy or hypersensitivity or other contraindication to any component of the chemotherapy regimen the participant may receive during the study
• Women who are pregnant, or breastfeeding
• Known targetable c-ROS oncogene 1 (ROS1) or BRAFV600E genomic aberration.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (128)

UCLA

Los Angeles, California, 90095, United States

Location

PIH Health Whittier Hospital

Whittier, California, 90602, United States

Location

SCRI Florida Cancer Specialists South

Fort Myers, Florida, 33901, United States

Location

SCRI Florida Cancer Specialists North

St. Petersburg, Florida, 33705, United States

Location

Advent Health Orlando

Winter Park, Florida, 32789, United States

Location

Northwest Georgia Oncology Centers PC - Marietta

Marietta, Georgia, 30060, United States

Location

Fort Wayne Medical Oncology and Hematology, Inc

Fort Wayne, Indiana, 46804, United States

Location

Baptist Health Lexington

Lexington, Kentucky, 40503, United States

Location

Tennessee Oncology Chattanooga

Chattanooga, Tennessee, 37403, United States

Location

Sarah Cannon Research Institute / Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

AZORG Campus Aalst-Moorselbaan

Aalst, 9300, Belgium

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

CHU UCL Mont-Godinne

Mont-godinne, 5530, Belgium

Location

Vitaz

Sint-Niklaas, 9100, Belgium

Location

Crio - Centro Regional Integrado de Oncologia

Fortaleza, Ceará, 60336-550, Brazil

Location

Oncocentro Belo Horizonte

Belo Horizonte, Minas Gerais, 30360-680, Brazil

Location

Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda

Ijuí, Rio Grande do Sul, 98700-000, Brazil

Location

Hospital das Clinicas - UFRGS

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Hospital Nossa Senhora da Conceicao

Porto Alegre, Rio Grande do Sul, 91350-200, Brazil

Location

Hospital de Cancer de Barretos

Barretos, São Paulo, 14784-400, Brazil

Location

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, 01246-000, Brazil

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Royal Victoria Regional Health Centre

Barrie, Ontario, L4M 6M2, Canada

Location

Lakeridge Health Oshawa

Oshawa, Ontario, L1G 2B9, Canada

Location

Sault Area Hospital

Sault Ste. Marie, Ontario, P6B 0A8, Canada

Location

Beijing Cancer Hospital

Beijing, 100142, China

Location

Jilin Cancer Hospital

Changchun, 132013, China

Location

Xiangya Hospital Central South University

Changsha, 410008, China

Location

Affiliated Hospital of Chengde Medical University

Chengde, 067020, China

Location

Sichuan Cancer Hospital

Chengdu, 610041, China

Location

West China Hospital - Sichuan University

Chengdu, 610047, China

Location

Anhui Provincial Hospital

Hefei, 230088, China

Location

Jinan Central Hospital

Jinan, 250013, China

Location

Pingxiang People's Hospital

Pingxiang, 337000, China

Location

Qingdao Central Hospital

Qingdao, 266042, China

Location

Weifang People's Hospital

Weifang, 261041, China

Location

Hubei Cancer Hospital

Wuhan, 430079, China

Location

The First Affiliated Hospital of Xian Jiao Tong University

Xi'an, 710061, China

Location

The First Affiliated Hospital of Xinxiang Medical University

Xinxiang, 453000, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, 450052, China

Location

Rigshospitalet

København Ø, 2100, Denmark

Location

Odense Universitetshospital, Onkologisk Afdeling R

Odense C, 5000, Denmark

Location

Sjællands Universitetshospital, Roskilde

Roskilde, 4000, Denmark

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Hopital Nord

Marseille, 13915, France

Location

Hopital de Pontchaillou

Rennes, 35033, France

Location

CHU Strasbourg - Nouvel Hopital Civil

Strasbourg, 67091, France

Location

CHU de Toulouse - Hôpital Larrey

Toulouse, 31100, France

Location

Helios Klinikum Emil von Behring GmbH

Berlin, 14165, Germany

Location

Klinikum Chemnitz gGmbH

Chemnitz, 09116, Germany

Location

St. Vincentius Kliniken Karlsruhe

Karlsruhe, 76137, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Medizinische Klinik, Pneumologie

Mainz, 55131, Germany

Location

Klinikum der Philipps-Universität Marburg

Marburg, 35032, Germany

Location

Hong Kong United Oncology Centre

Hong Kong, Hong Kong

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Tuen Mun Hospital

Hong Kong, Hong Kong

Location

Prince of Wales Hospital

Shatin, Hong Kong

Location

Centro Di Riferimento Oncologico

Aviano, Friuli Venezia Giulia, 33081, Italy

Location

A.O. Villa Scassi

Genoa, Liguria, 16149, Italy

Location

Azienda Ospedaliero-Universitaria Careggi

Florence, Tuscany, 50139, Italy

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

Kurume University Hospital

Fukuoka, 830-0011, Japan

Location

Hiroshima University Hospital

Hiroshima, 734-8551, Japan

Location

Takarazuka City Hospital

Hyōgo, 665-0827, Japan

Location

University Hospital Kyoto Prefectural University of Medicine

Kyoto, 602-8566, Japan

Location

Sendai Kousei Hospital

Miyagi, 981-0914, Japan

Location

Osaka International Cancer Institute

Osaka, 541-8567, Japan

Location

Kansai Medical University Hospital

Osaka, 573-1191, Japan

Location

Kindai University Hospital

Osaka, 589-8511, Japan

Location

NHO Kinki Chuo Chest Medical Center

Osaka, 591-8555, Japan

Location

Saitama Cancer Center

Saitama, 362-0806, Japan

Location

The Cancer Institute Hospital of JFCR

Tokyo, 135-8550, Japan

Location

Wakayama Medical University Hospital

Wakayama, 641-8510, Japan

Location

Health Pharma Professional Research

Mexico City, Mexico CITY (federal District), 03100, Mexico

Location

Cuidados oncologicos

Querétaro City, Querétaro, 76000, Mexico

Location

Oncologico Potosino

San Luis Potosí City, San Luis Potosí, 78209, Mexico

Location

ARKE Estudios Clínicos S.A. de C.V.

Mexico City, 06700, Mexico

Location

Auckland City Hospital, Cancer and Blood Research

Auckland, 1023, New Zealand

Location

Waikato Hospital - Cancer and Blood Research Trials Unit

Hamilton, 3204, New Zealand

Location

Palmerston North Hospital

Palmerston North, 4442, New Zealand

Location

Centrum Terapii Wspolczesnej J.M.Jasnorzewska Spolka Komandytowo-Akcyjna

Lódz, 90-338, Poland

Location

Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie

Olsztyn, 10-357, Poland

Location

Kosin University Gospel Hospital

Busan, 49267, South Korea

Location

Kyungpook National University Chilgok Hospital

Daegu, 41404, South Korea

Location

Chungnam National University Hospital

Daejeon, 35015, South Korea

Location

St. Vincent's Hospital

Gyeonggi-do, 16247, South Korea

Location

Samsung Changwon Hospital

Gyeongsangnam-do, 51353, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Kangbuk Samsung Hospital

Seoul, 03181, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Seoul St Mary's Hospital

Seoul, 06591, South Korea

Location

Hospital Son Llatzer

Palma de Mallorca, Balearic Islands, 07198, Spain

Location

ICO L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Complejo Hospitalario Universitario Insular?Materno Infantil

Las Palmas de Gran Canaria, LAS Palmas, 35016, Spain

Location

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, 15006, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Clinic Barcelona

Barcelona, 08036, Spain

Location

Hospital Lucus Augusti

Lugo, 27003, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Univ. Nuestra Señora de Valme

Seville, 41014, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Kantonsspital Aarau

Aarau, 5001, Switzerland

Location

Kantonsspital Graubünden Medizin Onkologie

Chur, 7000, Switzerland

Location

UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

Changhua Christian Hospital

Chang-hua, 500, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Vajira Hospital

Bangkok, 10300, Thailand

Location

Chulalongkorn Hospital

Bangkok, 10330, Thailand

Location

Faculty of Med. Siriraj Hosp.

Bangkok, 10700, Thailand

Location

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, 50200, Thailand

Location

Songklanagarind Hospital

Songkhla, 90110, Thailand

Location

Adana Baskent University Medical Faculty

Adana, 01220, Turkey (Türkiye)

Location

Ankara Bilkent City Hospital

Ankara, 06490, Turkey (Türkiye)

Location

Liv Hospital Ankara

Ankara, 06680, Turkey (Türkiye)

Location

Dicle University Faculty of Medicine

Diyarbakır, 21280, Turkey (Türkiye)

Location

Trakya University Medical Faculty

Edirne, 22030, Turkey (Türkiye)

Location

Istanbul University Cerrahpasa Medical Faculty

Istanbul, 34000, Turkey (Türkiye)

Location

Medeniyet University Goztepe Training and Research Hospital.

Kadiköy, 34722, Turkey (Türkiye)

Location

Castle Hill Hospital

Hull, HU16 5JQ, United Kingdom

Location

Barts & London School of Med

London, EC1A 7BE, United Kingdom

Location

Guy'S Hospital

London, SE1 9RT, United Kingdom

Location

Christie Hospital Nhs Trust

Manchester, M2O 4BX, United Kingdom

Location

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

New Cross Hospital

Wolverhampton, WV10 0QP, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Tiragolumab; atezolizumab; Pemetrexed; Carboplatin; Cisplatin; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2020
• First Posted: November 6, 2020
• Study Start: December 15, 2020
• Primary Completion: April 19, 2024
• Study Completion: November 20, 2025
• Last Updated: February 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

FR (5); TW (3); US (11); BR (7); PL (2); CH (3); BE (4); CA (4); ES (11); TH (5); JP (13); NZ (3); HK (4); KR (10); TU (7); CN (15); DK (3); DE (5); IT (3); GB (6); ME (4)