A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Gastric or Gastroesophageal Junction Carcinoma (MORPHEUS C-Gastric and Gastroesophageal Junction Carcinoma)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 40
- 试验地点
- 19
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Measurable disease according to RECIST v1.1
- •Adequate hematologic and end-organ function
- •Patients without hepatitis B virus (HBV) infection at screening
- •Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
- •Negative HIV test at screening
- •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
- •For men: agreement to remain abstinent or use contraception, and agreement to refrain from donating sperm, as outlined for each specific treatment arm
排除标准
- •for Stage 1:
- •Prior treatment with CD137 agonists or immune checkpoint blockade therapies
- •Treatment with investigational therapy within 28 days prior to initiation of study treatment
- •Any contraindications to any of the study drugs of the chemotherapy regimen
- •Eligible only for the control arm
- •Patients with a signet ring cells dominant carcinoma
- •Symptomatic, untreated, or actively progressing CNS metastases
- •History of leptomeningeal disease
- •Active or history of autoimmune disease or immune deficiency
- •Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
- •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
- •Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening
研究组 & 干预措施
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.
干预措施: Capecitabine (Drug)
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.
干预措施: Atezolizumab (Drug)
Atezo + CAPOX +Tira
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.
干预措施: Atezolizumab (Drug)
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.
干预措施: Oxaliplatin (Drug)
Atezo + CAPOX +Tira
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.
干预措施: Tiragolumab (Drug)
Atezo + CAPOX +Tira
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.
干预措施: Capecitabine (Drug)
Atezo + CAPOX +Tira
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.
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: 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.
Objective Response Rate (ORR)
时间窗: Up to 42.1 months
ORR was defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions, ≥ 4 weeks apart during Stage 1, as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target or non-target lesions. Any pathological lymph nodes (whether target or non-target lesions) must have a reduction in short axis to \< 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. Participants with missing or no response assessments were classified as non-responders. Percentages have been rounded off.
次要结局
- Overall Survival (OS)(At specific timepoints (up to approximately 3-5 years))
- 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))
- Percentage of Participants with Adverse Events in Stage 1(Baseline through approximately end of study (approximately 3-5 years))
- 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))
- Disease Control Rate(Up to approximately 3-5 years)
- Percentage of Participants with Adverse Events in Stage 2(Baseline through approximately end of study (approximately 3-5 years))
- Progression-free Survival (PFS) After Randomization(From randomization to first occurrence of PD or death from any cause, whichever occurred first (up to 42.1 months))
- Overall Survival (OS) After Randomization(From randomization to death from any cause (up to 42.1 months))
- OS Rates at Specified Timepoints(At Months 6 and 12)
- Duration of Response (DOR)(From first occurrence of CR or PR to PD or death from any cause, whichever occurred first (up to 42.1 months))
- Disease Control Rate (DCR)(Up to 42.1 months)
- Number of Participants With Adverse Events (AEs)(Up to 42.1 months)