A Phase 2 Trial to Evaluate the Safety and Efficacy of Combination Therapies in Patients With Advanced Upper Gastrointestinal Tract Malignancies (EDGE-Gastric)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 332
- 试验地点
- 43
- 主要终点
- Number of Participants with Adverse Events (AEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety and preliminary clinical activity of treatment combinations with and without chemotherapy in participants with locally advanced unresectable or metastatic gastric, GEJ, and esophageal adenocarcinoma. Chemotherapy will consist of FOLFOX (oxaliplatin, leucovorin, fluorouracil).
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
- •Participants with histologically confirmed diagnosis of locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma with life expectancy ≥3 months as assessed by the Investigator
- •Eastern cooperative oncology group (ECOG) Performance Score of 0-1
- •At least one measurable target lesion per RECIST v1.
- •Adequate organ and marrow function
- •Able to provide an archival tumor sample that is representative of the cancer under investigation and suitable for central PD-L1 testing
排除标准
- •Participants with underlying medical conditions that, in the Investigator's or Sponsor's opinion, will make the administration of investigational products hazardous
- •Only for Cohort A: Known Human Epidermal Growth Factor Receptor 2 (HER-2) positive tumor
- •Known untreated, symptomatic, or actively progressing central nervous system (brain) metastases. Participants with leptomeningeal metastases are excluded from enrollment.
- •Discontinued use of prior immune checkpoint therapy due to immune related adverse events; received prior treatment with an anti-TIGIT monoclonal antibody.
- •History of trauma or major surgery within 28 days prior to enrollment.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
A3 First Line - Treatment Naïve Participants
Non-randomized A3 safety run-in cohort: Domvanalimab and zimberelimab co-administered Q4W via IV infusion over 60 minutes in addition to FOLFOX chemotherapy via IV infusion Q2W.
After completion of A3 safety run-in cohort, participants are randomized to the A3 arm. Domvanalimab and zimberelimab co-administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX chemotherapy via IV infusion Q2W
干预措施: Leucovorin (Drug)
A3 First Line - Treatment Naïve Participants
Non-randomized A3 safety run-in cohort: Domvanalimab and zimberelimab co-administered Q4W via IV infusion over 60 minutes in addition to FOLFOX chemotherapy via IV infusion Q2W.
After completion of A3 safety run-in cohort, participants are randomized to the A3 arm. Domvanalimab and zimberelimab co-administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX chemotherapy via IV infusion Q2W
干预措施: Zimberelimab (Drug)
A1: First Line - Treatment Naïve Participants
Domvanalimab and zimberelimab once every 4 weeks (Q4W) in addition to FOLFOX chemotherapy by intravenous (IV) infusion once every 2 weeks (Q2W)
干预措施: Fluorouracil (Drug)
A3 First Line - Treatment Naïve Participants
Non-randomized A3 safety run-in cohort: Domvanalimab and zimberelimab co-administered Q4W via IV infusion over 60 minutes in addition to FOLFOX chemotherapy via IV infusion Q2W.
After completion of A3 safety run-in cohort, participants are randomized to the A3 arm. Domvanalimab and zimberelimab co-administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX chemotherapy via IV infusion Q2W
干预措施: Domvanalimab (Drug)
A1: First Line - Treatment Naïve Participants
Domvanalimab and zimberelimab once every 4 weeks (Q4W) in addition to FOLFOX chemotherapy by intravenous (IV) infusion once every 2 weeks (Q2W)
干预措施: Zimberelimab (Drug)
A4 First Line - Treatment Naïve Participants
Zimberelimab administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX chemotherapy via IV infusion Q2W
干预措施: Leucovorin (Drug)
B1: Second Line or greater Checkpoint Inhibitor Naïve Participants
Domvanalimab and zimberelimab administered once every three weeks (Q3W) by IV infusion
干预措施: Zimberelimab (Drug)
A1: First Line - Treatment Naïve Participants
Domvanalimab and zimberelimab once every 4 weeks (Q4W) in addition to FOLFOX chemotherapy by intravenous (IV) infusion once every 2 weeks (Q2W)
干预措施: Domvanalimab (Drug)
A1: First Line - Treatment Naïve Participants
Domvanalimab and zimberelimab once every 4 weeks (Q4W) in addition to FOLFOX chemotherapy by intravenous (IV) infusion once every 2 weeks (Q2W)
干预措施: Leucovorin (Drug)
A2: First Line - Treatment Naïve Participants
Zimberelimab Q4W in addition to chemotherapy with FOLFOX administered by IV infusion Q2W
干预措施: Zimberelimab (Drug)
A2: First Line - Treatment Naïve Participants
Zimberelimab Q4W in addition to chemotherapy with FOLFOX administered by IV infusion Q2W
干预措施: Oxaliplatin (Drug)
A2: First Line - Treatment Naïve Participants
Zimberelimab Q4W in addition to chemotherapy with FOLFOX administered by IV infusion Q2W
干预措施: Leucovorin (Drug)
A4 First Line - Treatment Naïve Participants
Zimberelimab administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX chemotherapy via IV infusion Q2W
干预措施: Zimberelimab (Drug)
B2: Second Line or greater Checkpoint Inhibitor Naïve Participants
Quemliclustat Q2W and zimberelimab Q4W administered by IV infusion
干预措施: Zimberelimab (Drug)
A1: First Line - Treatment Naïve Participants
Domvanalimab and zimberelimab once every 4 weeks (Q4W) in addition to FOLFOX chemotherapy by intravenous (IV) infusion once every 2 weeks (Q2W)
干预措施: Oxaliplatin (Drug)
A4 First Line - Treatment Naïve Participants
Zimberelimab administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX chemotherapy via IV infusion Q2W
干预措施: Oxaliplatin (Drug)
Cohort C1: Second Line or greater - Checkpoint Inhibitor Experienced Participants
Domvanalimab and zimberelimab Q3W administered by IV infusion
干预措施: Zimberelimab (Drug)
A3 First Line - Treatment Naïve Participants
Non-randomized A3 safety run-in cohort: Domvanalimab and zimberelimab co-administered Q4W via IV infusion over 60 minutes in addition to FOLFOX chemotherapy via IV infusion Q2W.
After completion of A3 safety run-in cohort, participants are randomized to the A3 arm. Domvanalimab and zimberelimab co-administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX chemotherapy via IV infusion Q2W
干预措施: Oxaliplatin (Drug)
B1: Second Line or greater Checkpoint Inhibitor Naïve Participants
Domvanalimab and zimberelimab administered once every three weeks (Q3W) by IV infusion
干预措施: Domvanalimab (Drug)
Cohort C1: Second Line or greater - Checkpoint Inhibitor Experienced Participants
Domvanalimab and zimberelimab Q3W administered by IV infusion
干预措施: Domvanalimab (Drug)
B2: Second Line or greater Checkpoint Inhibitor Naïve Participants
Quemliclustat Q2W and zimberelimab Q4W administered by IV infusion
干预措施: Quemliclustat (Drug)
A3 First Line - Treatment Naïve Participants
Non-randomized A3 safety run-in cohort: Domvanalimab and zimberelimab co-administered Q4W via IV infusion over 60 minutes in addition to FOLFOX chemotherapy via IV infusion Q2W.
After completion of A3 safety run-in cohort, participants are randomized to the A3 arm. Domvanalimab and zimberelimab co-administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX chemotherapy via IV infusion Q2W
干预措施: Fluorouracil (Drug)
A2: First Line - Treatment Naïve Participants
Zimberelimab Q4W in addition to chemotherapy with FOLFOX administered by IV infusion Q2W
干预措施: Fluorouracil (Drug)
A4 First Line - Treatment Naïve Participants
Zimberelimab administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX chemotherapy via IV infusion Q2W
干预措施: Fluorouracil (Drug)
结局指标
主要结局
Number of Participants with Adverse Events (AEs)
时间窗: Up to 18 months
Objective Response Rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
时间窗: Up to 18 months
次要结局
- Objective Response Rate (ORR) as measured by PD-L1 Expression Level(Up to 18 months)
- Overall survival (OS)(From date of first dose until the date of death due to any cause (approximately 18 months))
- Disease Control (complete response, partial response, or stable disease) for greater than equal to 12 weeks(Up to 18 months)
- Duration of response (DOR) as determined by the Investigator according to RECIST v1.1(Up to 18 months)
- Plasma concentration of zimberelimab(Up to 18 months)
- Plasma concentration of domvanalimab(Up to 18 months)
- Plasma concentration of quemliclustat(Up to 18 months)
- Percentage of participants with anti-drug antibodies to zimberelimab(Up to 18 months)
- Percentage of participants with anti-drug antibodies to domvanalimab(Up to 18 months)
- Progression-free survival (PFS) as determined by the Investigator according to RECIST v1.1(Up to 18 months)