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

Esophageal Cancer Clinical Trial

— SKYSCRAPER-08  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04540211
• Other study ID #: YO42138
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 30, 2020
• Est. completion date: August 14, 2025

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 461
• Est. completion date: August 14, 2025
• Est. primary completion date: February 13, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Esophageal Cancer

Intervention

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.
• Tiragolumab
Tiragolumab at a fixed dose of 600 mg administered by IV infusion every Q3W on Day 1 of each 21-day cycle.
• Paclitaxel
Paclitaxel 175 mg/m^2 administered by IV infusion on Day 1 of each 21-day cycle for 6 cycles.
• Cisplatin
Cisplatin 60-80 mg/m^2 administered by IV infusion on Day 1 of each 21-day cycle for 6 cycles.
• Atezolizumab Matching Placebo
Atezolizumab matching placebo administered by IV infusion, Q3W on Day 1 of each 21-day cycle.
• Tiragolumab Matching Placebo
Tiragolumab matching placebo administered by IV infusion, Q3W on Day 1 of each 21-day cycle.

Locations

Country	Name	City	State
China	Anyang Tumor Hosptial	Anyang City
China	Beijing Cancer Hospital	Beijing
China	Beijing Luhe Hospital Capital Medical University	Beijing City
China	Jilin Cancer Hospital	Changchun
China	the First Hospital of Jilin University	Changchun
China	Hunan Cancer Hospital	Changsha CITY
China	Affiliated Hospital of Chengde Medical University	Chengde City
China	Sichuan Provincial Cancer Hospital	Chengdu
China	West China Hospital, Sichuan University	Chengdu
China	Chongqing Sanxia Central Hospital	Chongqing City
China	The First People's Hospital of Foshan; Local Ethic Committee	Foshan
China	Fujian Cancer Hospital	Fuzhou
China	Fujian Provincial Hospital	Fuzhou City
China	Southern Medical University Nanfang Hospital	Guangdong Province Guangzhou City
China	Harbin Medical University Cancer Hospital	Harbin
China	Anhui Provincial Hospital	Hefei
China	The Second Affiliated Hospital of Anhui Medical University	Hefei
China	Anhui Province Cancer Hospital	Hefei City
China	Huai'an First People's Hospital	Huai'an City
China	The Second People's Hospital of Huai'an	Huai'an City
China	Affiliated Hopsital of Jining Medical University	Jining
China	Gansu Province People Hospital	Lanzhou
China	The First People's Hospital of Lian Yun Gang	Lianyungang
China	Linyishi Cancer Hospital	Linyi City
China	The First Affiliated Hospital to Henan University of Science and Technology	Luoyang City
China	Jiangsu Cancer Hospital	Nanjing City
China	Jiangsu Province Hospital of Chinese Medicine	Nanjing City
China	Nan Tong Tumor Hospital	Nantong City
China	Shanghai Chest Hospital	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai
China	Fudan University Shanghai Cancer Center	Shanghai City
China	Cancer Hospital of Shantou University Medical College	Shantou
China	Liaoning Provincial Cancer Hospital	Shengyang
China	The University of Hong Kong-Shenzhen Hospital; Local Ethic Committee	Shenzhen City
China	Suining Central Hospital	Suining
China	Tianjin Cancer Hospital	Tianjin
China	Weifang People's Hospital	Weifang City
China	Hubei Cancer Hospital	Wuhan
China	Wuhan Union Hospital Tongji Medical College, Huazhong University of Science and Technology	Wuhan City
China	Affiliated Hospital of Jiangnan University(Wuxi Fourth People's Hospital )	Wuxi City
China	First Affiliated Hospital of Medical College of Xi'an Jiaotong University	Xi'an
China	The Second Affiliated Hospital of The Fourth Military Medical University (Tangdu Hospital)	Xi'an
China	The First Affiliated Hospital of Xiamen University	Xiamen
China	Zhongshan Hospital Xiamen University	Xiamen
China	Xiangyang Central Hospital	Xiangyang
China	The First Affiliated Hospital of Xinxiang Medical University	Xinxiang City
China	Xuzhou Central Hospital	Xuzhou
China	Northern Jangsu People's Hospital	Yangzhou City
China	Zhejiang Cancer Hospital	Zhejiang
China	Henan Cancer Hospital	Zhengzhou
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou
Hong Kong	Queen Mary Hospital; Dept. of Clinical Oncology	Hong Kong
Hong Kong	Prince of Wales Hosp; Dept. Of Clinical Onc	Shatin
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Taiwan	Chang Gung Medical Foundation - Kaohsiung; Oncology	Kaohisung
Taiwan	National Cheng Kung University Hospital; Oncology	Tainan
Taiwan	Taipei Veterans General Hospital; Department of Oncology	Taipei City
Taiwan	National Taiwan University Hospital; Oncology	Zhongzheng Dist.
Thailand	Chulalongkorn Hospital; Medical Oncology	Bangkok
Thailand	Rajavithi Hospital; Division of Medical Oncology	Bangkok
Thailand	Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc	Bangkok
Thailand	Siriraj Hospital; Medical Oncology Unit	Bangkok
Thailand	Songklanagarind Hospital; Department of Oncology	Songkhla

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

China,  Hong Kong,  Korea, Republic of,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)		From randomization to death from any cause (up to approximately 35 months)
Primary	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	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)
Secondary	IRF-Assessed Confirmed Objective Response Rate (ORR)		From randomization up to approximately 35 months
Secondary	Investigator-Assessed Confirmed ORR		From randomization up to approximately 35 months
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Percentage of Participants With Adverse Events (AEs)		Up to approximately 35 months
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)