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 (SKYSCRAPER-07)

• ClinicalTrials.gov Identifier: NCT04543617
• Recruitment Status: Active, not recruiting
• First Posted: September 10, 2020
• Last Update Posted: April 26, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: September 3, 2020
• First Posted Date: September 10, 2020
• Last Update Posted Date: April 26, 2024
• Actual Study Start Date: September 28, 2020
• Estimated Primary Completion Date: March 31, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 2, 2023)

• Arm A vs Arm C: Investigator-Assessed Progression-Free Survival (PFS) [ Time Frame: 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) [ Time Frame: From randomization to death from any cause (up to approximately 6 years) ]
• Arm B vs Arm C: OS [ Time Frame: From randomization to death from any cause (up to approximately 6 years) ]

Original Primary Outcome Measures (submitted: September 3, 2020)

• Arm A vs Arm C: Investigator-Assessed Progression-Free Survival (PFS) [ Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 50 months) ]
• Arm A vs Arm C: Overall Survival (OS) [ Time Frame: From randomization to death from any cause (up to approximately 50 months) ]
• Arm B vs Arm C: OS [ Time Frame: From randomization to death from any cause (up to approximately 50 months) ]

Current Secondary Outcome Measures (submitted: November 2, 2023)

• Arm B vs Arm C: Investigator-Assessed PFS [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From randomization to death from any cause (up to approximately 6 years) ]
• Independent Review Facility (IRF)-Assessed PFS [ Time Frame: 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) [ Time Frame: From randomization up to approximately 6 years ]
• IRF-Assessed Confirmed ORR [ Time Frame: From randomization up to approximately 6 years ]
• Investigator-Assessed Duration of Objective Response (DOR) [ Time Frame: 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 6 years) ]
• IRF-Assessed DOR [ Time Frame: 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 6 years) ]
• Percentage of Participants With Clinically Meaningful Changes in Physical Functioning, Role Functioning, Quality of Life (QoL) as Measured by EORTC QLQ-C30 [ Time Frame: Up to approximately 6 years ]
  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.
• Percentage of Participants With Clinically Meaningful Changes in Dysphagia as Measured by EORTC QLQ-OES18 [ Time Frame: Up to approximately 6 years ]
  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.
• Percentage of Participants With Adverse Events (AEs) [ Time Frame: Up to approximately 6 years ]
• Serum Concentration of Tiragolumab [ Time Frame: Predose and postdose on Day 1 of Cycle 1 (each cycle=21 days) and predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 and at treatment discontinuation (TD) visit (up to approximately 6 years) ]
• Serum Concentration of Atezolizumab [ Time Frame: Predose and postdose on Day 1 of Cycle 1 (each cycle=21 days) and predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 6 years) ]
• Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab [ Time Frame: Predose on Day 1 of Cycles (each cycle=21 days) 1, 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 6 years) ]
• Percentage of Participants With ADAs to Atezolizumab [ Time Frame: Predose on Day 1 of Cycles (each cycle=21 days) 1, 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 6 years) ]

Original Secondary Outcome Measures (submitted: September 3, 2020)

• Arm B vs Arm C: Investigator-Assessed PFS [ Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 50 months) ]
• Arm A vs Arm B: Investigator-Assessed PFS [ Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 50 months) ]
• Arm A vs Arm B: OS [ Time Frame: From randomization to death from any cause (up to approximately 50 months) ]
• Independent Review Facility (IRF)-Assessed PFS [ Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 50 months) ]
• Investigator-Assessed Confirmed Objective Response Rate (ORR) [ Time Frame: From randomization up to approximately 50 months ]
• IRF-Assessed Confirmed ORR [ Time Frame: From randomization up to approximately 50 months ]
• Investigator-Assessed Duration of Objective Response (DOR) [ Time Frame: 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 50 months) ]
• IRF-Assessed DOR [ Time Frame: 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 50 months) ]
• Percentage of Participants With Clinically Meaningful Changes in Physical Functioning, Role Functioning, Quality of Life (QoL) as Measured by EORTC QLQ-C30 [ Time Frame: Up to approximately 50 months ]
  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.
• Percentage of Participants With Clinically Meaningful Changes in Dysphagia as Measured by EORTC QLQ-OES18 [ Time Frame: Up to approximately 50 months ]
  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.
• Percentage of Participants With Adverse Events (AEs) [ Time Frame: Up to approximately 50 months ]
• Serum Concentration of Tiragolumab [ Time Frame: Predose and postdose on Day 1 of Cycle 1 (each cycle=21 days) and predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 and at treatment discontinuation (TD) visit (up to approximately 50 months) ]
• Serum Concentration of Atezolizumab [ Time Frame: Predose and postdose on Day 1 of Cycle 1 (each cycle=21 days) and predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 50 months) ]
• Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab [ Time Frame: Predose on Day 1 of Cycles (each cycle=21 days) 1, 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 50 months) ]
• Percentage of Participants With ADAs to Atezolizumab [ Time Frame: Predose on Day 1 of Cycles (each cycle=21 days) 1, 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 50 months) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab With or Without Tiragolumab (Anti-TIGIT Antibody) in Patients With Unresectable Esophageal Squamous Cell Carcinoma Whose Cancers Have Not Progressed Following Definitive Concurrent Chemoradiotherapy
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Esophageal Squamous Cell Carcinoma

Intervention

• Drug: Tiragolumab
  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.
  Other Name: MTIG7192A, RO7092284
• Drug: Atezolizumab
  Atezolizumab at a fixed dose of 1200 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle.
  Other Name: Tecentriq, RO5541267
• Drug: Tiragolumab Matching Placebo
  Tiragolumab matching placebo administered by IV infusion Q3W on Day 1 of each 21-day cycle.
• Drug: Atezolizumab Matching Placebo
  Atezolizumab matching placebo administered by IV infusion Q3W on Day 1 of each 21-day cycle.

Study Arms

• Experimental: Arm A: Tiragolumab + Atezolizumab
  Participants will receive atezolizumab followed by tiragolumab.
  Interventions:

  • Drug: Tiragolumab
  • Drug: Atezolizumab
• Experimental: Arm B: Tiragolumab Placebo + Atezolizumab
  Participants will receive atezolizumab followed by tiragolumab matching placebo.
  Interventions:

  • Drug: Atezolizumab
  • Drug: Tiragolumab Matching Placebo
• Placebo Comparator: Arm C: Tiragolumab Placebo + Atezolizumab Placebo
  Participants will receive matching placebos to tiragolumab and atezolizumab.
  Interventions:

  • Drug: Tiragolumab Matching Placebo
  • Drug: Atezolizumab Matching Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 28, 2023): 760
• Original Estimated Enrollment (submitted: September 3, 2020): 750
• Estimated Study Completion Date: March 31, 2027
• Estimated Primary Completion Date: March 31, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• 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.

Key Exclusion Criteria:

• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, China, France, Germany, Greece, Hungary, Israel, Italy, Japan, Kenya, Korea, Republic of, Morocco, New Zealand, Poland, Portugal, Russian Federation, South Africa, Spain, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Brazil, Czechia

Administrative Information

• NCT Number: NCT04543617
• Other Study ID Numbers: YO42137; 2020-001178-31 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trial; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: April 2024