A Phase II, Single-Arm Study to Explore the Efficacy and Safety of Atezolizumab Plus Tiragolumab and Chemotherapy in 1st Line HER2 Negative Unresectable, Recurrent or Metastatic Gastric Cancer or Adenocarcinoma of Gastroesophageal Junction (GEJ)
Overview
- Phase
- Phase 2
- Intervention
- Atezolizumab
- Conditions
- Stomach Neoplasms
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 29
- Locations
- 11
- Primary Endpoint
- Objective Response Rate (ORR) in the Full Analysis Set (FAS) Population
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
This study is designed to evaluate the efficacy and safety of atezolizumab plus tiragolumab in combination with capecitabine plus oxaliplatin (XELOX) for first-line treatment in participants with HER2-negative unresectable advanced, recurrent or metastatic gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJ AC).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed (by enrolling center) gastric cancer or adenocarcinoma of GEJ (Siewert I-III)
- •Unresectable locally advanced, unresectable recurrent, or metastatic disease that meets the following criteria: a) No prior systemic treatment for advanced disease, b) For patients receiving prior chemoradiotherapy or chemotherapy in the adjuvant or neoadjuvant setting, with an interval of at least 6 months between the final treatment and the diagnosis of advanced disease
- •Measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as determined by investigator assessment
- •Availability of a representative tumor specimen that is suitable for determination of PD-L1 and TIGIT expression
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Life expectancy \>/=3 months
- •Adequate hematologic and end-organ function
- •For women of childbearing potential: agreement to refrain from heterosexual intercourse or use contraception, and agreement to refrain from donating eggs
- •For men: agreement to refrain from heterosexual intercourse or use contraceptive methods, and agreement to refrain from donating sperm.
Exclusion Criteria
- •HER2-positive by local review, defined as either immunohistochemistry (IHC) score of 3+ or IHC 2+ with amplification proven by in situ hybridization (ISH) as assessed based on pretreatment tumor tissues
- •Use of Chinese herbal medicine or Chinese patent medicines to control cancer within 7 days prior to initiation of study treatment
- •Higher risk of bleeding or fistula caused by GEJ Siewert I invading adjacent organs
- •Symptomatic, untreated, or actively progressing CNS metastases
- •Uncontrolled tumor-related pain
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
- •Uncontrolled or symptomatic hypercalcemia
- •Active or history of autoimmune disease or immune deficiency
- •History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
- •Severe chronic or active infection within 4 weeks prior to initiation of study treatment
Arms & Interventions
Atezo + Tira + XELOX
Atezolizumab plus tiragolumab in combination with XELOX (oxaliplatin and capecitabine) will be administered during Cycles 1-4 (each cycle is 21 days). During Cycle 5 and beyond atezolizumab and tiragolumab will be administered on Day 1 of each 21-day cycle. Participants will receive study treatment until disease progression, unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Intervention: Atezolizumab
Atezo + Tira + XELOX
Atezolizumab plus tiragolumab in combination with XELOX (oxaliplatin and capecitabine) will be administered during Cycles 1-4 (each cycle is 21 days). During Cycle 5 and beyond atezolizumab and tiragolumab will be administered on Day 1 of each 21-day cycle. Participants will receive study treatment until disease progression, unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Intervention: Tiragolumab
Atezo + Tira + XELOX
Atezolizumab plus tiragolumab in combination with XELOX (oxaliplatin and capecitabine) will be administered during Cycles 1-4 (each cycle is 21 days). During Cycle 5 and beyond atezolizumab and tiragolumab will be administered on Day 1 of each 21-day cycle. Participants will receive study treatment until disease progression, unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Intervention: Oxaliplatin
Atezo + Tira + XELOX
Atezolizumab plus tiragolumab in combination with XELOX (oxaliplatin and capecitabine) will be administered during Cycles 1-4 (each cycle is 21 days). During Cycle 5 and beyond atezolizumab and tiragolumab will be administered on Day 1 of each 21-day cycle. Participants will receive study treatment until disease progression, unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Intervention: Capecitabine
Outcomes
Primary Outcomes
Objective Response Rate (ORR) in the Full Analysis Set (FAS) Population
Time Frame: Up to approximately 20 months
Secondary Outcomes
- Mean Score in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire in Gastric Cancer (EORTC QLQ-STO22) in the FAS Population(Up to approximately 20 months)
- Progression-free Survival (PFS) in a Subgroup Population With PD-L1 and/or TIGIT Positive Expression(The time from initiation of study treatment to the first occurrence of disease progression or death from any cause (whichever occurs first) up to approximately 20 months)
- Change from Baseline in EORTC QLQ-STO22 in the FAS Population(Up to approximately 20 months)
- Duration of Response (DOR) in Responders of a Subgroup Population With PD-L1 and/or TIGIT Positive Expression(The time from the first occurrence of a confirmed objective response to the first occurrence of disease progression or death from any cause (whichever occurs first) up to approximately 20 months)
- Overall Survival (OS) in a Subgroup Population With PD-L1 and/or TIGIT Positive Expression(The time from initiation of study treatment to death due to any cause up to approximately 20 months)
- Overall Survival (OS) in the FAS Population(The time from initiation of study treatment to death due to any cause up to approximately 20 months)
- ORR in a Subgroup Population With PD-L1 and/or TIGIT Positive Expression(Up to approximately 20 months)
- Number of Participants With Adverse Events(Up to approximately 20 months)
- Progression-free Survival (PFS) in the FAS Population(The time from initiation of study treatment to the first occurrence of disease progression or death from any cause (whichever occurs first) up to approximately 20 months)
- Duration of Response (DOR) in Responders of the FAS Population(The time from the first occurrence of a confirmed objective response to the first occurrence of disease progression or death from any cause (whichever occurs first) up to approximately 20 months)
- Mean Score in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) in the FAS Population(Up to approximately 20 months)
- Change from Baseline in EORTC QLQ-C30 in the FAS Population(Up to approximately 20 months)