A Study of Atezolizumab With or Without Tiragolumab in Participants With Unresectable Esophageal Squamous Cell Carcinoma Whose Cancers Have Not Progressed Following Definitive Concurrent Chemoradiotherapy

NCT04543617 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: YO421372020-001178-31
• Study Type: interventional
• Target: 760
• Locations: 27 countries
• Sites: 163

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of tiragolumab plus atezolizumab compared with placebo in participants with unresectable esophageal squamous cell carcinoma (or those who are unable or unwilling to undergo surgery) and whose cancers have not progressed following definitive concurrent chemoradiotherapy (dCRT). Participants will be randomized in a 1:1:1 ratio to receive either tiragolumab plus atezolizumab (Arm A), tiragolumab matching placebo plus atezolizumab (Arm B), or double placebo (Arm C).

Conditions

Esophageal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (3)

• Arm A vs Arm C: Investigator-Assessed Progression-Free Survival (PFS)

  From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 6 years)

• Arm A vs Arm C: Overall Survival (OS)

  From randomization to death from any cause (up to approximately 6 years)

• Arm B vs Arm C: OS

  From randomization to death from any cause (up to approximately 6 years)

Secondary Outcomes (15)

• Arm B vs Arm C: Investigator-Assessed PFS

  From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 6 years)

• Arm A vs Arm B: Investigator-Assessed PFS

  From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 6 years)

• Arm A vs Arm B: OS

  From randomization to death from any cause (up to approximately 6 years)

• Independent Review Facility (IRF)-Assessed PFS

  From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 6 years)

• Investigator-Assessed Confirmed Objective Response Rate (ORR)

  From randomization up to approximately 6 years

Study Arms (3)

Arm A: Tiragolumab + Atezolizumab

EXPERIMENTAL

Participants will receive atezolizumab followed by tiragolumab.

Drug: Tiragolumab; Drug: Atezolizumab

Arm B: Tiragolumab Placebo + Atezolizumab

EXPERIMENTAL

Participants will receive atezolizumab followed by tiragolumab matching placebo.

Drug: Atezolizumab; Drug: Tiragolumab Matching Placebo

Arm C: Tiragolumab Placebo + Atezolizumab Placebo

PLACEBO COMPARATOR

Participants will receive matching placebos to tiragolumab and atezolizumab.

Drug: Tiragolumab Matching Placebo; Drug: Atezolizumab Matching Placebo

Interventions

Tiragolumab Matching Placebo DRUG

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

Arm B: Tiragolumab Placebo + Atezolizumab; Arm C: Tiragolumab Placebo + Atezolizumab Placebo

Atezolizumab Matching Placebo DRUG

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

Arm C: Tiragolumab Placebo + Atezolizumab Placebo

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, RO7092284

Arm A: Tiragolumab + Atezolizumab

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, RO5541267

Arm A: Tiragolumab + Atezolizumab; Arm B: Tiragolumab Placebo + Atezolizumab

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 confirmed diagnosis of squamous cell carcinoma of the esophagus
• Unresectable disease ineligible for curative surgery based on the documented opinion of the qualified medical, surgical or radiation oncologist prior to dCRT and is not expected to undergo tumor resection during the course of the study
• dCRT treatment according to regional oncology guidelines for esophageal cancer
• Representative archival formalin-fixed, paraffin-embedded (FFPE) tumor specimens collected prior to initiation of dCRT
• Adequate hematologic and end-organ function prior to randomization
• Women of childbearing potential must remain abstinent or use contraceptive methods with a failure rate of \< 1% per year during the treatment period, for 5 months after the final dose of atezolizumab/placebo, and for 90 days after the final dose of tiragolumab/placebo, whichever is later
• Men must agree to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm during the treatment period and for 90 days after the final dose of tiragolumab/placebo.

You may not qualify if:

• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, anti-PD-L1 and anti-TIGIT therapeutic antibodies
• Any unresolved toxicity of National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2 from the prior chemoradiation therapy with the exception of irreversible and manageable hearing loss
• Prior allogeneic stem cell or solid organ transplantation
• Active or history of autoimmune disease or immune deficiency
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
• Malignancies other than esophageal cancer within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
• Treatment with any other investigational agent, including epidermal growth factor receptor (EGFR) inhibitors, with therapeutic intent for esophageal cancer prior to randomization.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (167)

Florida Cancer Specialists - Fort Myers (Broadway)

Fort Myers, Florida, 33901, United States

Location

Cancer Center of Kansas

Wichita, Kansas, 67214-3728, United States

Location

Great Lakes Cancer Center

Williamsville, New York, 14221, United States

Location

Instituto de Investigaciones Metabolicas (Idim)

Buenos Aires, C1012AAR, Argentina

Location

Fundacion Favaloro

Buenos Aires, C1093AAS, Argentina

Location

Centro Oncologico Riojano Integral (CORI)

La Rioja, F5300COE, Argentina

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

St John of God Hospital

Subiaco, Western Australia, 6008, Australia

Location

Tiroler Landeskrankenanstalten Ges.M.B.H.

Innsbruck, 6020, Austria

Location

Klinikum Klagenfurt am Wörthersee

Klagenfurt, 9020, Austria

Location

Ordensklinikum Linz Barmherzige Schwestern

Linz, 4010, Austria

Location

AKH - Medizinische Universität Wien

Vienna, 1090, Austria

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

CHU de Liège (Sart Tilman)

Liège, 4000, Belgium

Location

Anyang Tumor Hosptial

Anyang, 455000, China

Location

Cancer Hospital Chinese Academy of Medical Sciences.

Beijing, 100021, China

Location

Affiliated Hospital of Bengbu Medical College

Bengbu, 233004, China

Location

Hunan Cancer Hospital

Changsha, 410013, China

Location

Heping Hospital Affiliated to Changzhi Medical College

Changzhi, 046000, China

Location

Changzhou Cancer hospital

Changzhou, 213000, China

Location

Sichuan Provincial Cancer Hospital

Chengdu, 610041, China

Location

West China Hospital, Sichuan University

Chengdu, 610041, China

Location

Chongqing Cancer Hospital

Chongqing, 400030, China

Location

Chongqing Sanxia Central Hospital

Chongqing, 404000, China

Location

Fujian Cancer Hospital

Fuzhou, 350014, China

Location

Sun Yet-sen University Cancer Center

Guangzhou, 510060, China

Location

Nanfang Hospital, Southern Medical University

Guangzhou, 510515, China

Location

Zhejiang Cancer Hospital

Hangzhou, 310022, China

Location

Jieyang People's Hospital

Jieyang, China

Location

Shandong Cancer Hospital

Jinan, 250117, China

Location

Affiliated Hospital of Jining Medical University

Jining, 272029, China

Location

The First People's Hospital of Lian Yun Gang

Lianyungang, 222002, China

Location

Lishui Central Hospital

Lishui, China

Location

The First Affiliated Hospital to Henan University of Science and Technology

Luoyang, 471003, China

Location

Affiliated Drum Tower Hospital of Nanjing University Medical School

Nanjing, 210008, China

Location

Shanghai Chest Hospital

Shanghai, 200000, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

Location

Cancer Hospital of Shantou University Medical College

Shantou, 515041, China

Location

Liaoning cancer Hospital & Institute

Shenyang, 110042, China

Location

Cancer Hospital Chinese Academy of Medical Sciences Shenzhen Center

Shenzhen, China

Location

Hebei Medical University Fourth Hospital

Shijiazhuang, 050035, China

Location

Tianjin Cancer Hospital

Tianjin, 300060, China

Location

Wuhan Union Hospital Tongji Medical College, Huazhong University of Science and Technology

Wuhan, 430022, China

Location

Hubei Cancer Hospital

Wuhan, 430079, China

Location

The First Affiliated Hospital of Xiamen University

Xiamen, 361003, China

Location

Zhongshan Hospital Xiamen University

Xiamen, 361004, China

Location

The First Affiliated Hospital of Xinxiang Medical University

Xinxiang, China

Location

The Affiliated Hospital of Xuzhou Medical College

Xuzhou, 221000, China

Location

Subei People's Hospital of Jiangsu province

Yangzhou, 225001, China

Location

CHRU De Brest - Hopital Morvan - Institut De Cancerologie Et D'Hematologie

Brest, 29609, France

Location

CHU Dijon Bourgogne Hôpital François Mitterand

Dijon, 21000, France

Location

Hopital Claude Huriez

Lille, 59037, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Hopital Timone Adultes

Marseille, 13385, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

European Hospital Georges Pompidou (HEGP)

Paris, 75908, France

Location

Hopital Du Haut-Leveque

Pessac, 33604, France

Location

Chu La Miletrie

Poitiers, 86021, France

Location

Hopital Rangueil

Toulouse, 31059, France

Location

Universitätsklinikum Essen Klinik f.Strahlentherapie

Essen, 45122, Germany

Location

Kliniken Essen-Mitte, Evang. Huyssens-Stiftung, Klinik für Internistische Onkologie / Haematologie

Essen, 45136, Germany

Location

Klinik für Gastroenterologie und Gastrointestinale Onkologie der UMG

Göttingen, 37075, Germany

Location

Universitaetsklinikum Leipzig

Leipzig, 04103, Germany

Location

Med. Fak. d. Otto-von-Guericke-Universität

Magdeburg, 39120, Germany

Location

Klinikum der Philipps-Universität Marburg

Marburg, 35032, Germany

Location

Universitätsklinikum Klinik u.Poliklinik f.Strahlentherapie

Regensburg, 93053, Germany

Location

Evgenidio Hospital "Agia Trias"

Athens, 115 28, Greece

Location

Univ General Hosp Heraklion

Heraklion, 711 10, Greece

Location

Euromedical General Clinic of Thessaloniki

Thessaloniki, 546 45, Greece

Location

Pécsi Tudományegyetem

Pécs, 7623, Hungary

Location

Szegedi Tudományegyetem

Szeged, 6720, Hungary

Location

Hadassah Ein Karem Hospital

Jerusalem, 9112000, Israel

Location

Rambam Health Corporation

Rambam, 3525408, Israel

Location

Tel Aviv Sourasky Medical Ctr

Tel Aviv, 6423906, Israel

Location

Università degli Studi della Campania Luigi Vanvitelli

Naples, Campania, 80131, Italy

Location

Ospedale Degli Infermi - Faenza

Faenza, Emilia-Romagna, 48018, Italy

Location

Asu Fc S. M. Della Misericordia

Udine, Friuli Venezia Giulia, 33100, Italy

Location

Istituto Oncologico Veneto IRCCS

Padova, Veneto, 35128, Italy

Location

Aichi Cancer Center Hospital

Aichi, 464-8681, Japan

Location

National Cancer Center Hospital East

Chiba, 277-8577, Japan

Location

Hiroshima University Hospital

Hiroshima, 734-8551, Japan

Location

Kobe University Hospital

Hyōgo, 650-0017, Japan

Location

Yokohama City University Medical Center

Kanagawa, 232-0024, Japan

Location

Kanagawa Cancer Center

Kanagawa, 241-8515, Japan

Location

Tohoku University Hospital

Miyagi, 980-8574, Japan

Location

Niigata Cancer Center Hospital

Niigata, 951-8566, Japan

Location

Osaka International Cancer Institute

Osaka, 541-8567, Japan

Location

The University of Osaka Hospital

Osaka, 565-0871, Japan

Location

Saitama Medical University International Medical Center

Saitama, 350-1298, Japan

Location

Saitama Cancer Center

Saitama, 362-0806, Japan

Location

Shizuoka Cancer Center

Shizuoka, 411-8777, Japan

Location

The Cancer Institute Hospital of JFCR

Tokyo, 135-8550, Japan

Location

Keio University Hospital

Tokyo, 160-8582, Japan

Location

International Cancer Institute (ICI)

Eldoret, 30100, Kenya

Location

The Aga Khan University-Kenya.

Nairobi, 00100, Kenya

Location

Centre Hospitalier Universitaire Hassan II

Fes, 30000, Morocco

Location

Centre Hospitalier Universitaire Mohamed VI

Marrakesh, 40000, Morocco

Location

Institut National D'oncologie Sidi Med Benabdellah

Rabat, 10100, Morocco

Location

Tauranga Hospital, Clinical Trials Unit

Tauranga, 3112, New Zealand

Location

Centrum Onkologii

Bydgoszcz, 85-796, Poland

Location

Centrum Onkologii Ziemi Lubelskiej Im. ?W. Jana Z Dukli

Lublin, 20-090, Poland

Location

Szpital Kliniczny MSWiA z Warmi?sko-Mazurskim Centrum Onkologii

Olsztyn, 10-228, Poland

Location

Wielkopolskie Centrum Onkologii im. Marii Sk?odowskiej-Curie

Późna, 61-866, Poland

Location

NIO im Marii Sklodowskiej-Curie

Warsaw, 02-034, Poland

Location

Dolno?l?skie Centrum Onkologii

Wroc?aw, 53-413, Poland

Location

HUC

Coimbra, 3000-075, Portugal

Location

Centro Hospitalar do Porto ? Hospital de Santo António

Porto, 4099-001, Portugal

Location

IPO do Porto

Porto, 4200-072, Portugal

Location

Krasnoyarsk Regional Oncology Dispensary n.a. Krizhanovsky

Krasnoyarsk, Krasnodarskiy Kray, 660133, Russia

Location

Russian Oncology Research Center n.a. N.N. Blokhin Dpt of Clinical Pharmacology and Chemotherapy

Moscow, Moscow Oblast, 115478, Russia

Location

Scientific Research Institute n.a. N.N. Petrov

Saint Petersburg, Sankt-Peterburg, 187758, Russia

Location

SBEI HPE "The First St.Petersburg State Medical University n.a. acad. I.P.Pavlova"of MoH of RF

Saint Petersburg, Sankt-Peterburg, 197022, Russia

Location

Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic

Kazan', Tatarstan Republic, 420029, Russia

Location

City Oncological Hospital

Izhevsk, Udmurtiya Republic, 426067, Russia

Location

Limited Liability Company "RC Medical"

Novosibirsk, 630005, Russia

Location

Regional Oncology Dispensary

Tomsk, 634063, Russia

Location

Limpopo Cancer Research Institute

Polokwane, South Africa

Location

Cancercare

Port Elizabeth, 6045, South Africa

Location

Eugene Marais Hospital

Pretoria, South Africa

Location

Kyungpook National University Chilgok Hospital

Daegu, 41404, South Korea

Location

Ajou University Medical Center

Gyeonggi-do, 16499, South Korea

Location

Chonnam National University Hwasun Hospital

Jeollanam-do, 58128, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Korea University Guro Hospital

Seoul, 08308, South Korea

Location

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, LA Coruna, 15006, Spain

Location

Hospital Univ. Central de Asturias

Oviedo, Principality of Asturias, 33006, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic I Provincial

Barcelona, 08036, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Regional Universitario Carlos Haya

Málaga, 29010, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital La Fe

Valencia, Spain

Location

Inselspital Bern, Insel-Gruppe AG

Bern, 3010, Switzerland

Location

UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

Chang Gung Medical Foundation - Kaohsiung;Oncology

Kaohisung, Taiwan

Location

China Medical University Hospital

Taichung, 404, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 00704, Taiwan

Location

Chi-Mei Medical Centre

Tainan, 710, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112201, Taiwan

Location

Vajira Hospital

Bangkok, 10300, Thailand

Location

Chulalongkorn Hospital

Bangkok, 10330, Thailand

Location

Ramathibodi Hospital

Bangkok, 10400, Thailand

Location

Siriraj Hospital

Bangkok, 10700, Thailand

Location

Songklanagarind Hospital

Songkhla, 90110, Thailand

Location

Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital

Adana, 01250, Turkey (Türkiye)

Location

Ankara University Faculty of Medicine Cebeci Hospital

Ankara, 06700, Turkey (Türkiye)

Location

Ankara City Hospital

Ankara, 06800, Turkey (Türkiye)

Location

Ataturk University Medical Faculty Yakutiye Research Hospital Medical Oncology Department

Erzurum, 25240, Turkey (Türkiye)

Location

Goztepe Prof.Dr. Suleyman Yalcin City Hospital

Kadiköy, 34722, Turkey (Türkiye)

Location

Inonu University Faculty of Medicine Turgut Ozal Medical Center

Malatya, 44280, Turkey (Türkiye)

Location

Van Yuzuncu Yil University Hospital

Van, Turkey (Türkiye)

Location

Municipal Noncommercial Institution Regional Center of Oncology

Kharkiv, Kharkiv Governorate, 61070, Ukraine

Location

Zhytomyr Regional Oncology Center

Zhytomyr, KIEV Governorate, Ukraine

Location

Vinnytsya Regional Clinical Oncology Dispensary

Vinnytsia, Podolia Governorate, 21029, Ukraine

Location

RCI Sumy Regional Clinical Oncological Dispensary

Sumy, 40005, Ukraine

Location

Royal Bournemouth Hospital

Bournemouth, BH7 7DW, United Kingdom

Location

Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Ninewells Hospital

London, DD1 9SY, United Kingdom

Location

Royal Marsden Hospital - Fulham

London, SW3 6JJ, United Kingdom

Location

Clatterbridge Cancer Centre

Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

Location

Royal Marsden Hospital (Sutton)

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Tiragolumab; atezolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Clinical Trial

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: September 3, 2020
• First Posted: September 10, 2020
• Study Start: September 28, 2020
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

ES (9); IT (4); AU (3); IL (3); US (3); TW (6); NZ (1); PT (3); ZA (3); UA (4); TH (5); FR (10); JP (15); RU (8); GB (6); CN (35); TU (7); KR (7); PL (6); HU (2); MO (3); CH (2); BE (3); KE (2); AR (3); GR (3); DE (7)