A Study of Atezolizumab Plus Tiragolumab in Combination With Paclitaxel and Cisplatin Compared With Paclitaxel and Cisplatin as First-Line Treatment in Participants With Unresectable Locally Advanced, Unresectable Recurrent, or Metastatic Esophageal Carcinoma (SKYSCRAPER-08)

A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab Plus Tiragolumab in Combination With Paclitaxel and Cisplatin Compared With Paclitaxel and Cisplatin as First-Line Treatment in Patients With Unresectable Locally Advanced, Unresectable Recurrent, or Metastatic Esophageal Squamous Cell Carcinoma

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Esophageal Cancer
• Intervention / Treatment: Drug: Atezolizumab; Drug: Tiragolumab; Drug: Paclitaxel; Drug: Cisplatin; Drug: Atezolizumab Matching Placebo; Drug: Tiragolumab Matching Placebo

• Study Type: Interventional
• Enrollment (Actual): 461
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anyang City, China, 455000
    • Anyang Tumor Hosptial
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Beijing City, China, 101100
    • Beijing Luhe Hospital Capital Medical University
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Changchun, China, 132013
    • Jilin Cancer Hospital
  • Changsha CITY, China, 410013
    • Hunan Cancer Hospital
  • Chengde City, China, 067020
    • Affiliated Hospital of Chengde Medical University
  • Chengdu, China, 610041
    • West China Hospital, Sichuan University
  • Chengdu, China, 610041
    • Sichuan Provincial Cancer Hospital
  • Chongqing City, China, 404000
    • Chongqing Sanxia Central Hospital
  • Foshan, China, 510000
    • The First People's Hospital of Foshan; Local Ethic Committee
  • Fuzhou, China, 350014
    • Fujian Cancer Hospital
  • Fuzhou City, China, 350001
    • Fujian Provincial Hospital
  • Guangdong Province Guangzhou City, China, 510515
    • Southern Medical University Nanfang Hospital
  • Harbin, China, 150081
    • Harbin Medical University Cancer Hospital
  • Hefei, China, 230001
    • Anhui Provincial Hospital
  • Hefei, China, 230601
    • The Second Affiliated Hospital of Anhui Medical University
  • Hefei City, China, 230031
    • Anhui Province Cancer Hospital
  • Huai'an City, China, 223300
    • Huai'an First People's Hospital
  • Huai'an City, China, 223300
    • The Second People's Hospital of Huai'an
  • Jining, China, 272000
    • Affiliated Hopsital of Jining Medical University
  • Lanzhou, China, 730000
    • Gansu Province People Hospital
  • Lianyungang, China, 222023
    • The First People's Hospital of Lian Yun Gang
  • Linyi City, China, 276034
    • Linyishi Cancer Hospital
  • Luoyang City, China, 471031
    • The First Affiliated Hospital to Henan University of Science and Technology
  • Nanjing City, China, 211100
    • Jiangsu Cancer Hospital
  • Nanjing City, China, 210029
    • Jiangsu Province Hospital of Chinese Medicine
  • Nantong City, China, 226361
    • Nan Tong Tumor Hospital
  • Shanghai, China, 200000
    • Shanghai Chest Hospital
  • Shanghai, China, 200032
    • Zhongshan Hospital Fudan University
  • Shanghai City, China, 200120
    • Fudan University Shanghai Cancer Center
  • Shantou, China, 515041
    • Cancer Hospital of Shantou University Medical College
  • Shengyang, China, 110042
    • Liaoning Provincial Cancer Hospital
  • Shenzhen City, China, 518053
    • The University of Hong Kong-Shenzhen Hospital; Local Ethic Committee
  • Suining, China, 629000
    • Suining Central Hospital
  • Tianjin, China, 300060
    • Tianjin Cancer Hospital
  • Weifang City, China, 261041
    • WeiFang People's Hospital
  • Wuhan, China, 430079
    • Hubei Cancer Hospital
  • Wuhan City, China, 430022
    • Wuhan Union Hospital Tongji Medical College, Huazhong University of Science and Technology
  • Wuxi City, China, 214062
    • Affiliated Hospital of Jiangnan University(Wuxi Fourth People's Hospital )
  • Xi'an, China, 710061
    • First Affiliated Hospital of Medical College of Xi'an Jiaotong University
  • Xi'an, China, 710038
    • The Second Affiliated Hospital of The Fourth Military Medical University (Tangdu Hospital)
  • Xiamen, China, 361003
    • The First Affiliated Hospital of Xiamen University
  • Xiamen, China, 361004
    • Zhongshan Hospital Xiamen University
  • Xiangyang, China
    • Xiangyang Central Hospital
  • Xinxiang City, China, 453000
    • The First Affiliated Hospital of Xinxiang Medical University
  • Xuzhou, China, 221000
    • XuZhou Central Hospital
  • Yangzhou City, China, 225001
    • Northern Jangsu People's Hospital
  • Zhejiang, China, 310022
    • Zhejiang Cancer Hospital
  • Zhengzhou, China, 450008
    • Henan Cancer Hospital
  • Zhengzhou, China, 450052
    • The First Affiliated Hospital of Zhengzhou University
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital; Dept. of Clinical Oncology
  • Shatin, Hong Kong
    • Prince of Wales Hosp; Dept. Of Clinical Onc
• Korea, Republic of
  • Daegu, Korea, Republic of, 41404
    • Kyungpook National University Chilgok Hospital
  • Goyang-si, Korea, Republic of, 10408
    • National Cancer Center
  • Seongnam-si, Korea, Republic of, 463-707
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 08308
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• Taiwan
  • Kaohisung, Taiwan, 833
    • Chang Gung Medical Foundation - Kaohsiung; Oncology
  • Tainan, Taiwan, 00704
    • National Cheng Kung University Hospital; Oncology
  • Taipei City, Taiwan, 112201
    • Taipei Veterans General Hospital; Department of Oncology
  • Zhongzheng Dist., Taiwan, 10048
    • National Taiwan University Hospital; Oncology
• Thailand
  • Bangkok, Thailand, 10330
    • Chulalongkorn Hospital; Medical Oncology
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc
  • Bangkok, Thailand, 10400
    • Rajavithi Hospital; Division of Medical Oncology
  • Bangkok, Thailand, 10700
    • Siriraj Hospital; Medical Oncology Unit
  • Songkhla, Thailand, 90110
    • Songklanagarind Hospital; Department of Oncology

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• 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

Key Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atezolizumab + Tiragolumab + PC; 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: Atezolizumab; 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.; Other Names: Tecentriq; Drug: Tiragolumab; Tiragolumab at a fixed dose of 600 mg administered by IV infusion every Q3W on Day 1 of each 21-day cycle.; Other Names: MTIG7192A; Drug: Paclitaxel; Paclitaxel 175 mg/m^2 administered by IV infusion on Day 1 of each 21-day cycle for 6 cycles.; Drug: Cisplatin; Cisplatin 60-80 mg/m^2 administered by IV infusion on Day 1 of each 21-day cycle for 6 cycles.
Placebo Comparator: Placebo + PC; 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: Paclitaxel; Paclitaxel 175 mg/m^2 administered by IV infusion on Day 1 of each 21-day cycle for 6 cycles.; Drug: Cisplatin; Cisplatin 60-80 mg/m^2 administered by IV infusion on Day 1 of each 21-day cycle for 6 cycles.; Drug: Atezolizumab Matching Placebo; Atezolizumab matching placebo administered by IV infusion, Q3W on Day 1 of each 21-day cycle.; Drug: Tiragolumab Matching Placebo; Tiragolumab matching placebo administered by IV infusion, Q3W on Day 1 of each 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Survival (OS)	From randomization to death from any cause (up to approximately 35 months)
Independent Review Facility (IRF)-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 35 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-Assessed PFS		From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 35 months)
IRF-Assessed Confirmed Objective Response Rate (ORR)		From randomization up to approximately 35 months
Investigator-Assessed Confirmed ORR		From randomization up to approximately 35 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 35 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 35 months)
Time to Confirmed Deterioration (TTCD) in Participant-Reported Physical Functioning, Role Functioning and Global Health Status (GHS)/Quality of Life (QoL) as Measured by EORTC QLQ-C30	Clinically meaningful changes in physical functioning, role functioning, global health status (GHS)/QoL as measured by the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30). EORTC QLQ-C30 is a self-reported measure, consisting of 30 questions that assess 5 aspects of participants functioning (physical, emotional, role, cognitive and social), 3 symptom scales (fatigue, nausea and vomiting, and pain), GHS and QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) within the previous week. Functioning and symptoms items are scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. GHS and QoL items are scored on a 7-point scale: 1=Very poor, 2, 3, 4, 5, 6, 7=Excellent. Scores will be linearly transformed to a range of 0 to 100, with higher scores (i.e. closer to 100) reflecting better functioning, better GHS/QoL, and worse symptoms.	From randomization until the first confirmed clinically meaningful deterioration (up to approximately 35 months)
TTCD in Participant-Reported Dysphagia as Measured by EORTC QLQ-OES18	Clinically meaningful changes in dysphagia as measured by the EORTC Quality of Life-Esophageal Cancer, Module 18 Questionnaire (EORTC QLQ-OES18). EORTC QLQ-OES18 is a modular supplement to the EORTC QLQ-C30 questionnaire for use in participants with esophageal cancer. EORTC QLQ-OES18 consists of 4 multiple-item scale (dysphagia, eating, reflux, and pain) and 6 single items (trouble swallowing saliva, choked when swallowing, dry mouth, trouble with taste, trouble with coughing, and trouble talking) with a recall period of the previous week. Each symptom item is scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores will be linearly transformed to a range of 0 to 100, with higher transformed scores (i.e. closer to 100) reflecting worse symptoms.	From randomization until the first confirmed clinically meaningful deterioration (up to approximately 35 months)
Percentage of Participants With Adverse Events (AEs)		Up to approximately 35 months
Minimum Serum Concentration (Cmin) of Tiragolumab		Cycle 1 (cycle=21 days), Day 1: predose, 0.5 hour (h) postdose; Cycles 2, 3, 4, 8, 12, 16, Day 1: predose and at treatment discontinuation (TD) visit (up to approximately 35 months)
Maximum Serum Concentration (Cmax) of Tiragolumab		Cycle 1 (cycle=21 days), Day 1: predose, 0.5h postdose; Cycles 2, 3, 4, 8, 12, 16: Day 1: predose and at TD visit (up to approximately 35 months)
Cmin of Atezolizumab		Cycle 1 (cycle=21 days): Day 1 (predose, 0.5 h postdose); Cycles 2, 3, 4, 8, 12, 16: Day 1 (predose) and at TD visit (up to approximately 35 months)
Cmax of Atezolizumab		Cycle 1 (cycle=21 days): Day 1 (predose, 0.5 h postdose); Cycles 2, 3, 4, 8, 12, 16: Day 1 (predose) and at TD visit (up to approximately 35 months)
Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab		Predose on Day 1 of Cycles (cycle=21 days) 1, 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 35 months)
Percentage of Participants With ADAs to Atezolizumab		Predose on Day 1 of Cycles (cycle=21 days) 1, 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 35 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): October 30, 2020
• Primary Completion (Actual): February 13, 2023
• Study Completion (Estimated): August 14, 2025

Study Registration Dates

• First Submitted: September 3, 2020
• First Submitted That Met QC Criteria: September 3, 2020
• First Posted (Actual): September 7, 2020

Study Record Updates

• Last Update Posted (Actual): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Paclitaxel; Antibodies, Monoclonal; Atezolizumab
• Other Study ID Numbers: YO42138

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
• product manufactured in and exported from the U.S.: Yes