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)

Roche

Status and phase: Active, not recruiting; Phase 3

Conditions: Esophageal Squamous Cell Carcinoma

Treatments: Drug: Atezolizumab; Drug: Atezolizumab Matching Placebo; Drug: Tiragolumab; Drug: Tiragolumab Matching Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04543617

2020-001178-31 (EudraCT Number)

YO42137

Details and patient eligibility

About

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).

Enrollment: 760 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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760 participants in 3 patient groups, including a placebo group

Arm A: Tiragolumab + Atezolizumab

Experimental group

Description:

Participants will receive atezolizumab followed by tiragolumab.

Treatment:

Drug: Tiragolumab

Drug: Atezolizumab

Arm B: Tiragolumab Placebo + Atezolizumab

Experimental group

Description:

Participants will receive atezolizumab followed by tiragolumab matching placebo.

Treatment:

Drug: Tiragolumab Matching Placebo

Drug: Atezolizumab

Arm C: Tiragolumab Placebo + Atezolizumab Placebo

Placebo Comparator group

Description:

Participants will receive matching placebos to tiragolumab and atezolizumab.

Treatment:

Drug: Tiragolumab Matching Placebo

Drug: Atezolizumab Matching Placebo