NCT04540211

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of atezolizumab plus tiragolumab in combination with paclitaxel and cisplatin (PC) compared with atezolizumab matching placebo plus tiragolumab matching placebo plus PC as first-line treatment in participants with unresectable locally advanced, unresectable recurrent, or metastatic esophageal carcinoma (EC). Participants will be randomized in a 1:1 ratio to receive one of the following treatment regimens during induction phase: Arm A: Atezolizumab plus Tiragolumab and PC Arm B: Atezolizumab placebo plus Tiragolumab placebo and PC Following the induction phase, participants will continue maintenance therapy with either atezolizumab plus tiragolumab (Arm A) or atezolizumab matching placebo plus tiragolumab matching placebo (Arm B).

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
461

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Oct 2020

Longer than P75 for phase_3

Geographic Reach
5 countries

68 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 3, 2020

Completed
4 days until next milestone

First Posted

Study publicly available on registry

September 7, 2020

Completed
2 months until next milestone

Study Start

First participant enrolled

October 30, 2020

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 13, 2023

Completed
2.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 28, 2025

Completed
7 months until next milestone

Results Posted

Study results publicly available

April 9, 2026

Completed
Last Updated

April 9, 2026

Status Verified

March 1, 2026

Enrollment Period

2.3 years

First QC Date

September 3, 2020

Results QC Date

February 6, 2026

Last Update Submit

March 20, 2026

Conditions

Outcome Measures

Primary Outcomes (2)

  • Independent Review Facility (IRF)-Assessed Progression-Free Survival (PFS)

    PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause (whichever occurred first), as determined by an IRF according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm).

    From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 19 months)

  • Overall Survival (OS)

    OS was defined as the time from randomization to death from any cause.

    From randomization to death from any cause (up to approximately 27 months)

Secondary Outcomes (16)

  • Investigator-Assessed PFS

    From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 19 months)

  • IRF-Assessed Confirmed Objective Response Rate (ORR)

    From randomization up to approximately 19 months

  • Investigator-Assessed Confirmed ORR

    From randomization up to approximately 19 months

  • IRF-Assessed Duration of Objective Response (DOR)

    From the first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 19 months)

  • Investigator-Assessed DOR

    From the first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 19 months)

  • +11 more secondary outcomes

Study Arms (2)

Atezolizumab + Tiragolumab + PC

EXPERIMENTAL

Participants will receive atezolizumab and tiragolumab on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase.

Drug: AtezolizumabDrug: TiragolumabDrug: PaclitaxelDrug: Cisplatin

Placebo + PC

PLACEBO COMPARATOR

Participants will receive atezolizumab matching placebo and tiragolumab matching placebo on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase.

Drug: PaclitaxelDrug: CisplatinDrug: Atezolizumab Matching PlaceboDrug: Tiragolumab Matching Placebo

Interventions

Atezolizumab at a fixed dose of 1200 milligrams (mg) administered by intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.

Also known as: Tecentriq
Atezolizumab + Tiragolumab + PC

Tiragolumab at a fixed dose of 600 mg administered by IV infusion every Q3W on Day 1 of each 21-day cycle.

Also known as: MTIG7192A
Atezolizumab + Tiragolumab + PC

Paclitaxel 175 mg/m\^2 administered by IV infusion on Day 1 of each 21-day cycle for 6 cycles.

Atezolizumab + Tiragolumab + PCPlacebo + PC

Cisplatin 60-80 mg/m\^2 administered by IV infusion on Day 1 of each 21-day cycle for 6 cycles.

Atezolizumab + Tiragolumab + PCPlacebo + PC

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

Placebo + PC

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

Placebo + PC

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically confirmed EC
  • Unresectable locally advanced, unresectable recurrent, or metastatic disease
  • Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Adequate hematologic and end-organ function
  • Female participants must be willing to avoid pregnancy and refrain from donating eggs during the treatment period and for 90 days after the final dose
  • Male participants with partners of childbearing potential must commit to the use of two methods of contraception and must not donate sperm for the study duration and 90 days after the final dose

You may not qualify if:

  • Palliative radiation treatment for EC within 4 weeks prior to initiation of study treatment
  • Evidence of complete esophageal obstruction not amenable to treatment
  • Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
  • Uncontrolled tumor-related pain, uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
  • Active or history of autoimmune disease or immune deficiency or leptomeningeal disease
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
  • Malignancies other than EC within 2 years prior to screening with a negligible risk of metastasis or death adequately treated with expected curative outcome
  • 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
  • Positive test result for human immunodeficiency virus (HIV)
  • Active hepatitis B or hepatitis C
  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-CTLA-4, anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies
  • Treatment with any investigational therapy prior to initiation of study treatment
  • Poor peripheral venous access
  • Prior allogeneic stem cell or solid organ transplantation
  • Concurrent participation in another therapeutic clinical trial

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (68)

Anhui Provincial Hospital

Anhui, 230001, China

Location

Anyang Tumor Hosptial

Anyang, 455000, China

Location

Beijing Cancer Hospital

Beijing, 100142, China

Location

Beijing Luhe Hospital Capital Medical University

Beijing, China

Location

the First Hospital of Jilin University

Changchun, 130021, China

Location

Jilin Cancer Hospital

Changchun, 132013, China

Location

Hunan Cancer Hospital

Changsha, 410013, China

Location

Affiliated Hospital of Chengde Medical University

Chengde, 067020, China

Location

Sichuan Provincial Cancer Hospital

Chengdu, 610041, China

Location

West China Hospital, Sichuan University

Chengdu, 610041, China

Location

Chongqing Sanxia Central Hospital

Chongqing, 404000, China

Location

The First People's Hospital of Foshan

Foshan, 510000, China

Location

Fujian Cancer Hospital

Fuzhou, 350014, China

Location

Fujian Provincial Hospital

Fuzhou, China

Location

Southern Medical University Nanfang Hospital

Guangdong Province Guangzhou City, 510515, China

Location

Zhejiang Cancer Hospital

Hangzhou, 310022, China

Location

Harbin Medical University Cancer Hospital

Harbin, 150081, China

Location

Anhui Province Cancer Hospital

Hefei, 12345, China

Location

The Second Affiliated Hospital of Anhui Medical University

Hefei, 230601, China

Location

Huai'an First People's Hospital

Huai'an, China

Location

The Second People's Hospital of Huai'an

Huai'an, China

Location

Affiliated Hopsital of Jining Medical University

Jining, China

Location

Gansu Province People Hospital

Lanzhou, 730000, China

Location

The First People's Hospital of Lian Yun Gang

Lianyungang, 222002, China

Location

Linyishi Cancer Hospital

Linyi, 276034, China

Location

The First Affiliated Hospital to Henan University of Science and Technology

Luoyang, 471003, China

Location

Jiangsu Province Hospital of Chinese Medicine

Nanjing, 210029, China

Location

Jiangsu Cancer Hospital

Nanjing, 211100, China

Location

Nan Tong Tumor Hospital

Nantong, 226361, China

Location

Shanghai Chest Hospital

Shanghai, 200000, China

Location

Zhongshan Hospital Fudan University

Shanghai, 200032, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200120, China

Location

Cancer Hospital of Shantou University Medical College

Shantou, 515041, China

Location

Liaoning Provincial Cancer Hospital

Shengyang, 110042, China

Location

Suining Central Hospital

Suining, 629000, China

Location

Tianjin Cancer Hospital

Tianjin, 300060, China

Location

Weifang People's Hospital

Weifang, 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

Affiliated Hospital of Jiangnan University(Wuxi Fourth People's Hospital )

Wuxi, 214122, China

Location

The Second Affiliated Hospital of The Fourth Military Medical University (Tangdu Hospital)

Xi'an, 710038, China

Location

First Affiliated Hospital of Medical College of Xi'an Jiaotong University

Xi'an, 710061, China

Location

The First Affiliated Hospital of Xiamen University

Xiamen, 361003, China

Location

Zhongshan Hospital Xiamen University

Xiamen, 361004, China

Location

Xiangyang Central Hospital

Xiangyang, China

Location

The First Affiliated Hospital of Xinxiang Medical University

Xinxiang, China

Location

Xuzhou Central Hospital

Xuzhou, China

Location

Northern Jangsu People's Hospital

Yangzhou, 225001, China

Location

Henan Cancer Hospital

Zhengzhou, 450008, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, 450052, China

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Prince of Wales Hosp

Shatin, Hong Kong

Location

Kyungpook National University Chilgok Hospital

Daegu, 41404, South Korea

Location

National Cancer Center

Goyang-si, 10408, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, 13605, 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

Chang Gung Medical Foundation - Kaohsiung

Kaohisung, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 00704, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112201, Taiwan

Location

National Taiwan University Hospital

Zhongzheng Dist., 10048, Taiwan

Location

Chulalongkorn Hospital

Bangkok, 10330, Thailand

Location

Rajavithi Hospital

Bangkok, 10400, Thailand

Location

Ramathibodi Hospital

Bangkok, 10400, Thailand

Location

Siriraj Hospital

Bangkok, 10700, Thailand

Location

Songklanagarind Hospital

Songkhla, 90110, Thailand

Location

Related Publications (2)

  • Sun JM, Chao Y, Kim SB, Rha SY, Evans TRJ, Strickland AH, Wainberg Z, Chau I, Pelles-Avraham S, Ajani J, Malhotra R, Liu Q, Li S, Cha E, Kalaitzidou M, Huang X, Allen S, Hsu CH. First-line tiragolumab plus atezolizumab and chemotherapy in patients with previously untreated, locally advanced unresectable or metastatic oesophageal cancer (MORPHEUS-EC): a randomised, open-label, phase 1b/2 trial. Lancet Oncol. 2026 Jan;27(1):90-102. doi: 10.1016/S1470-2045(25)00402-4.

  • Hsu CH, Lu Z, Gao S, Wang J, Sun JM, Liu T, Fan Q, Cai J, Ge F, Li S, Zhang L, Cha E, Allen S, Shen L. Tiragolumab plus atezolizumab and chemotherapy as first-line treatment for patients with unresectable oesophageal squamous cell carcinoma (SKYSCRAPER-08): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2026 Jan;27(1):103-115. doi: 10.1016/S1470-2045(25)00401-2.

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

atezolizumabTiragolumabPaclitaxelCisplatin

Condition Hierarchy (Ancestors)

Gastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsHead and Neck NeoplasmsDigestive System DiseasesEsophageal DiseasesGastrointestinal Diseases

Intervention Hierarchy (Ancestors)

TaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenesChlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum Compounds

Results Point of Contact

Title
Medical Communications
Organization
Hoffmann-La Roche

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

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 7, 2020

Study Start

October 30, 2020

Primary Completion

February 13, 2023

Study Completion

August 28, 2025

Last Updated

April 9, 2026

Results First Posted

April 9, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will share

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

Locations