A Phase 2/3 Trial to Evaluate Margetuximab in Combination With INCMGA00012 and Chemotherapy or MGD013 and Chemotherapy in Patients With Metastatic or Locally Advanced, Treatment-naïve, HER2-Positive Gastric or Gastroesophageal Junction Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- MacroGenics
- 入组人数
- 82
- 试验地点
- 73
- 主要终点
- Number of Participants With Adverse Events of Margetuximab Plus Retifanlimab in Cohort A, as Assessed by CTCAE v5.0
研究概览
简要总结
This is a Phase 2/3, randomized, open-label study for the treatment of patients with HER2-positive Gastric cancer (GC) or Gastroesophageal Junction (GEJ) cancer conducted in two parts.
Part A is a single-arm cohort (Cohort A, 40 to 110 participants) will evaluate safety and efficacy of margetuximab plus retifanlimab.
Part B Part 1 has 4 arms (50 patients/arm). Participants will be randomized to margetuximab plus retifanlimab plus chemotherapy, margetuximab plus tebotelimab, plus chemotherapy, margetuximab plus chemotherapy, or trastuzumab plus chemotherapy.
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
- •Histologically confirmed diagnosis of previously untreated locally advanced unresectable or metastatic HER2+ GC or GEJ adenocarcinoma
- •Prior systemic perioperative treatment is allowed; however the participants must have had a disease-free interval of at least 6 months from end of chemo/surgery
- •Participants receiving perioperative anti-HER2 therapy require testing of HER2 status for eligibility
- •Cohort A: HER2-positive (by IHC 3+) and PD-L1-positive (by IHC with 22C3 CPS ≥ 1%) per central review
- •Cohort B: HER2-positive (by IHC 3+ or IHC 2+ in combination with FISH+) by local review. PD -L1 status is not required for enrollment.
- •Availability of formalin-fixed, paraffin-embedded tumor specimen, unstained slides or contemporaneous biopsy for tumor target testing
- •Eastern Cooperative Oncology Group performance status of 0 or 1, verified within 3 days of Day 1
- •Life expectancy ≥ 6 months
- •At least one radiographically measurable target lesion
- •Acceptable laboratory parameters and adequate organ function
排除标准
- •Other malignancy that is progressing or required treatment within the past 5 years, with certain exceptions
- •Participants with known MSI-H status
- •History of allogeneic stem cell or tissue/solid organ transplant
- •Central nervous system metastases
- •Clinically significant cardiovascular disease, gastrointestinal disorders, pulmonary compromise
- •Prior neoadjuvant or adjuvant treatment with immunotherapy
研究组 & 干预措施
Chemotherapy-free arm
margetuximab plus retifanlimab
干预措施: margetuximab (Biological)
Chemotherapy-free arm
margetuximab plus retifanlimab
干预措施: Retifanlimab (Biological)
Margetuximab, retifanlimab, and chemotherapy arm
margetuximab plus retifanlimab plus investigator choice of chemotherapy options.
Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)
干预措施: margetuximab (Biological)
Margetuximab, retifanlimab, and chemotherapy arm
margetuximab plus retifanlimab plus investigator choice of chemotherapy options.
Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)
干预措施: Retifanlimab (Biological)
Margetuximab, retifanlimab, and chemotherapy arm
margetuximab plus retifanlimab plus investigator choice of chemotherapy options.
Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)
干预措施: Chemotherapy (Other)
Margetuximab, tebotelimab and chemotherapy arm
margetuximab plus tebotelimab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)
干预措施: margetuximab (Biological)
Margetuximab, tebotelimab and chemotherapy arm
margetuximab plus tebotelimab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)
干预措施: Tebotelimab (Biological)
Margetuximab, tebotelimab and chemotherapy arm
margetuximab plus tebotelimab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)
干预措施: Chemotherapy (Other)
Margetuximab and chemotherapy arm
margetuximab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)
干预措施: margetuximab (Biological)
Margetuximab and chemotherapy arm
margetuximab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)
干预措施: Chemotherapy (Other)
Trastuzumab and chemotherapy arm
Trastuzumab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)
干预措施: Trastuzumab (Biological)
Trastuzumab and chemotherapy arm
Trastuzumab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)
干预措施: Chemotherapy (Other)
结局指标
主要结局
Number of Participants With Adverse Events of Margetuximab Plus Retifanlimab in Cohort A, as Assessed by CTCAE v5.0
时间窗: Throughout the study, an average of 11 months.
Evaluation of adverse events and serious adverse events (Cohort A)
Objective Response Rate (ORR) for Non-microsatellite Instability-high (Non-MSI-H) Participants (Cohort A) Using Investigator-assessed Radiology Reviews
时间窗: Throughout the study, an average of 11 months.
Percent of non MSI-H participants with best overall response of complete response (CR) plus partial response (PR) per RECIST 1.1 (Cohorts A ) based on investigator assessment. CR is defined as the disappearance of all target and non-target lesions with no new lesions appearing PR is defined as \>= to a 30% decrease in the sum of the longest dimensions of target lesions, non-progression of non- target lesions, with no new lesions appearing. CR + PR = ORR
次要结局
- Median Progression-free Survival Using Investigator-assessed Radiology Reviews in Cohort A(Throughout the study, an average of 11 months.)
- Median Duration of Response in Cohort A Using Investigator-assessed Radiology Reviews(Throughout the study, an average of 11 months.)
- Disease Control Rate(Throughout the study, an average of 11 months.)
- ORR for Cohort B(Throughout the study, an average of 11 months.)
- Number of Participants Who Have Antidrug Antibodies (ADA) to Margetuximab(Throughout the study, an average of 11 months.)
- Number of Participants Who Have ADA to Retifanlimab(Throughout the study, an average of 11 months.)
- Number of Participants Who Have ADA to Tebotelimab(Throughout the study, an average of 11 months.)