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Trial record 1 of 1 for:    NCT04543617
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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)

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

Study Description
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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).

Condition or disease Intervention/treatment Phase
Esophageal Squamous Cell Carcinoma Drug: Tiragolumab Drug: Atezolizumab Drug: Tiragolumab Matching Placebo Drug: Atezolizumab Matching Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 760 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : September 28, 2020
Estimated Primary Completion Date : March 31, 2027
Estimated Study Completion Date : March 31, 2027

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm A: Tiragolumab + Atezolizumab
Participants will receive atezolizumab followed by tiragolumab.
 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
Experimental: Arm B: Tiragolumab Placebo + Atezolizumab
Participants will receive atezolizumab followed by tiragolumab matching placebo.
 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.
Placebo Comparator: Arm C: Tiragolumab Placebo + Atezolizumab Placebo
Participants will receive matching placebos to tiragolumab and atezolizumab.
 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.


Outcome Measures
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Primary Outcome Measures :
  1. 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) ]
  2. Arm A vs Arm C: Overall Survival (OS) [ Time Frame: From randomization to death from any cause (up to approximately 6 years) ]
  3. Arm B vs Arm C: OS [ Time Frame: From randomization to death from any cause (up to approximately 6 years) ]

Secondary Outcome Measures :
  1. 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) ]
  2. 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) ]
  3. Arm A vs Arm B: OS [ Time Frame: From randomization to death from any cause (up to approximately 6 years) ]
  4. 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) ]
  5. Investigator-Assessed Confirmed Objective Response Rate (ORR) [ Time Frame: From randomization up to approximately 6 years ]
  6. IRF-Assessed Confirmed ORR [ Time Frame: From randomization up to approximately 6 years ]
  7. 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) ]
  8. 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) ]
  9. 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.

  10. 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.

  11. Percentage of Participants With Adverse Events (AEs) [ Time Frame: Up to approximately 6 years ]
  12. 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) ]
  13. 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) ]
  14. 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) ]
  15. 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) ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04543617


Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trial Hoffmann-La Roche
More Information
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04543617    
Other Study ID Numbers: YO42137
2020-001178-31 ( EudraCT Number )
First Posted: September 10, 2020    Key Record Dates
Last Update Posted: April 26, 2024
Last Verified: April 2024
Individual Participant Data (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).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Esophageal 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
Atezolizumab
Antibodies, Monoclonal
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs