An Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Gastric or Gastroesophageal Junction Carcinoma
Study Details
Study Description
Brief Summary
This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with advanced gastric carcinoma (GC) or gastroesophageal junction carcinoma (GEJC). The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, and modify the participant population. Cohort 1 will enroll participants with inoperable locally advanced, metastatic, or advanced GC or GEJC, with adenocarcinoma confirmed as the predominant histology, who have not received prior systemic therapy for advanced or metastatic disease. Eligible participants will initially be randomly assigned to one of treatment arms (Stage 1). Participants who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to receive treatment with a different treatment combination (Stage 2). When a Stage 2 treatment combination is available, this will be introduced by amending the protocol.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Atezo + CAPOX (capecitabine + oxaliplatin) Participants in the atezolizumab plus capecitabine plus oxaliplatin in Stage 1 will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator. |
Drug: Atezolizumab
Atezolizumab is administered by IV infusion on Day 1 of each 21 day cycle. Treatment until progressive disease.
Other Names:
Drug: Capecitabine
Capecitabine is administered orally twice daily on Days 1-14 of each 21 day cycle. Treatment for up to six cycles.
Drug: Oxaliplatin
Oxaliplatin is administered by IV infusion on Day 1 of each 21 day cycle. Treatment for up to six cycles.
|
| Experimental: Atezo + CAPOX +Tir Participants in the atezolizumab plus capecitabine plus oxaliplatin plus tiragolumab arm in Stage 1 will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator. |
Drug: Atezolizumab
Atezolizumab is administered by IV infusion on Day 1 of each 21 day cycle. Treatment until progressive disease.
Other Names:
Drug: Capecitabine
Capecitabine is administered orally twice daily on Days 1-14 of each 21 day cycle. Treatment for up to six cycles.
Drug: Oxaliplatin
Oxaliplatin is administered by IV infusion on Day 1 of each 21 day cycle. Treatment for up to six cycles.
Drug: Tiragolumab
Tiragolumab is administered by IV infusion on Day 1 of each 21 day cycle.
|
Outcome Measures
Primary Outcome Measures
- Objective Response Rate (ORR) [Up to approximately 3-5 years]
ORR is defined as the proportion of participants with a complete response or a partial response on two consecutive occasions >= 4 weeks apart during Stage 1, as determined by the investigator according to RECIST v1.1.
Secondary Outcome Measures
- Progression-Free Survival (PFS) [Randomization to the first occurrence of disease progression or death from any cause (whichever occurs first) (up to approximately 3-5 years)]
PFS after randomization is defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first) in Stage 1, as determined by the investigator according to RECIST v1.1.
- Overall Survival (OS) [Randomization to death from any cause (up to approximately 3-5 years)]
OS after randomization, defined as the time from randomization to death from any cause in Stage 1.
- Overall Survival (OS) [At specific timepoints (up to approximately 3-5 years)]
OS at specific timepoints in Stage 1.
- Duration of Response (DOR) [First occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first) (up to approximately 3-5 years)]
DOR is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first) in Stage 1, as determined by the investigator according to RECIST v1.1.
- Disease Control [Up to approximately 3-5 years]
Disease control is defined as stable disease for >= 12 weeks or a complete or a partial response, as determined by the investigator according to RECIST v1.1 in Stage 1.
- Objective Response [Up to approximately 3-5 years]
Objective response in participants with PD-L1-positive and/or TIGIT-positive tumors, as assessed by IHC in Stage 1.
- Percentage of Participants with Adverse Events [Baseline through approximately end of study (approximately 3-5 years)]
Percentage of participants with adverse events in Stage 1.
- Percentage of Participants with Adverse Events [Baseline through approximately end of study (approximately 3-5 years)]
Percentage of participants with adverse events in Stage 2.
Eligibility Criteria
Criteria
Inclusion Criteria for Stage 1:
-
ECOG Performance Status of 0 or 1
-
Inoperable locally advanced, metastatic, or advanced GC or GEJC, with adenocarcinoma confirmed as the predominant histology
-
No prior systemic treatment for advanced or metastatic disease
-
Life expectancy >= 3 months, as determined by the investigator
-
Human epidermal growth factor receptor 2 (HER2)-negative tumors
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Measurable disease according to RECIST v1.1
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Adequate hematologic and end-organ function
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Patients without hepatitis B virus (HBV) infection at screening
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Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
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Negative HIV test at screening
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For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs, as outlined for each specific treatment arm
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For men: agreement to remain abstinent or use contraception, and agreement to refrain from donating sperm, as outlined for each specific treatment arm
Exclusion Criteria for Stage 1:
-
Prior treatment with CD137 agonists or immune checkpoint blockade therapies
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Treatment with investigational therapy within 28 days prior to initiation of study treatment
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Any contraindications to any of the study drugs of the chemotherapy regimen
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Eligible only for the control arm
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Patients with a signet ring cells dominant carcinoma
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Symptomatic, untreated, or actively progressing CNS metastases
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History of leptomeningeal disease
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Active or history of autoimmune disease or immune deficiency
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Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
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History of malignancy other than GC or GEJC within 2 years prior to initiation of study treatment, with the exception of malignancies with a negligible risk of metastasis or death
Exclusion Criteria for Tiragolumab-Containing Arm:
-
Prior treatment with an anti-TIGIT agent
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Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The General Hospital of People's Liberation Army (301 Hospital) | Beijing City | China | 100080 | |
| 2 | First Affiliated Hospital of Gannan Medical University | Ganzhou | China | 341000 | |
| 3 | The Sixth Affiliated Hospital of Sun Yat-sen University | Guangzhou | China | 510655 | |
| 4 | The First Affiliated Hospital, Zhejiang University | Hangzhou City | China | 310003 | |
| 5 | Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University | Hangzhou | China | 310016 | |
| 6 | The Second Affiliated Hospital of Anhui Medical University | Hefei | China | 230601 | |
| 7 | Affiliated Hopsital of Jining Medical University | Jining | China | 272000 | |
| 8 | Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School | Nanjing City | China | 210008 | |
| 9 | Nan Tong Tumor Hospital | Nantong City | China | 226361 | |
| 10 | Shanxi Province Cancer Hospital | Taiyuan City | China | 030013 | |
| 11 | First Affiliated Hospital of Medical College of Xi'an Jiaotong University | Xi'an | China | 710061 | |
| 12 | The First Affiliated Hospital of Zhengzhou University | Zhengzhou | China | 450052 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- YO43408