A Phase 1b/2, Open Label, Dose Escalation Study of Margetuximab in Combination With Pembrolizumab in Patients With Relapsed/Refractory Advanced HER2+ Gastroesophageal Junction or Gastric Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- MacroGenics
- 入组人数
- 95
- 试验地点
- 28
- 主要终点
- Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs).
研究概览
简要总结
This main purpose of this clinical study is to learn about the safety and activity of margetuximab and pembrolizumab combination treatment in patients with HER2+ gastric and gastroesophageal junction cancer.
详细描述
Detailed Description: Both margetuximab and pembrolizumab are monoclonal antibodies used in combination to treat HER2+ gastric and gastroesophageal junction cancer. This study has two parts: Dose Escalation and Dose Expansion. The Dose Escalation phase of the study will evaluate safety of escalating doses of the combination treatment. The Dose Expansion phase will evaluate safety and activity of the combination in patients with gastric or gastroesophageal cancer once the final dose and schedule are defined. In addition, a cohort of patients with HER2+ 3+ gastric cancer patients will be enrolled in the Dose Expansion Phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Signed written informed consent.
- •Age ≥ 18 years old (or minimum age based upon local regulations)
- •Unresectable locally advanced or metastatic histologically proven HER2+ gastroesophageal junction (GEJ) or gastric cancer. Gastric Cancer Expansion Phase will include only gastric cancer patients with 3+ HER2 positivity.
- •HER2+ as 3+ (as defined in AJCC staging manual 8th edition) by IHC or in-situ hybridation (ISH) amplified.
- •Have received prior treatment with trastuzumab.
- •Have received treatment with at least one or more lines of cytotoxic chemotherapy in the metastatic setting.
- •Resolution of chemotherapy, immunotherapy or radiation-related toxicities.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy ≥ 12 weeks.
- •Measurable disease as per RECIST 1.1 criteria.
排除标准
- •Patients with symptomatic central nervous system (CNS) metastases.
- •Patients with any history of known or suspected autoimmune disease with the specific exceptions of vitiligo, atopic dermatitis, or psoriasis not requiring systemic treatment.
- •History of prior allogeneic bone marrow, stem-cell or solid organ transplantation.
- •Treatment with any systemic anti-neoplastic therapy, or investigational therapy within the 3 weeks prior to the initiation of study drug.
- •Treatment with radiation therapy within 3 weeks prior to the initiation of study drug administration.
- •Treatment with corticosteroids (≥10 mg per day prednisone or equivalent) or other immune suppressive drugs within the 14 days prior to the initiation of study drug administration.
- •History of clinically-significant cardiovascular disease.
- •Clinically-significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation.
- •History of (non-infectious) pneumonitis that required steroids or presence of active pneumonitis
- •Clinically-significant gastrointestinal disorders, such as perforation, gastrointestinal bleeding, or diverticulitis.
- •Evidence of active viral, bacterial, or systemic fungal infection.
研究组 & 干预措施
Cohort 1: Margetuximab 10 mg/kg plus pembrolizumab 200 mg
margetuximab administered in combination with pembrolizumab
干预措施: Margetuximab 10 mg/kg (Biological)
Cohort 1: Margetuximab 10 mg/kg plus pembrolizumab 200 mg
margetuximab administered in combination with pembrolizumab
干预措施: Pembrolizumab (Biological)
Cohort 2: Margetuximab 15 mg/kg plus pembrolizumab 200 mg
margetuximab administered in combination with pembrolizumab
干预措施: Margetuximab 15 mg (Biological)
Cohort 2: Margetuximab 15 mg/kg plus pembrolizumab 200 mg
margetuximab administered in combination with pembrolizumab
干预措施: Pembrolizumab (Biological)
结局指标
主要结局
Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs).
时间窗: up to 24 months
The number of patients that experience either an AE or a SAE during the study participation
Number of Patients With a Complete Response (CR) or Partial Response (PR) to Treatment Using irRC Criteria
时间窗: 12 Months
Investigate the preliminary anti-tumor activity, as measured by objective response rate (ORR) of margetuximab when administered in combination with pembrolizumab, using immune-related response criteria (irRC).
Number of Patients With Dose Limiting Toxicities
时间窗: 21 days
Characterize maximum tolerated dose (MTD) or maximum administered dose (MAD) (if no MTD is defined) of margetuximab when administered in combination with pembrolizumab
Number of Patients With a Complete Response (CR) or Partial Response (PR) to Treatment
时间窗: 12 months
Investigate the preliminary anti-tumor activity as measured by response to treatment of margetuximab when administered in combination with pembrolizumab, using conventional Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Duration of Response
时间窗: up to 24 months
Duration of response is calculated at the time from CR or PR to relapse or cancer progression.
次要结局
- Overall Survival (OS)(24 Months)
- Terminal Half-life(Predose and at end of infusion on Cycle 1, Days 1, 2 and 8: Cycle 2, Day 1; Cycle 3, Days 1 and 2; Cycle 5 Day 1, Cycle 7 Day 1, and end of treatment visit average 12 months .)
- Number of Patients Who Develop Treatment-emergent Anti-drug Antibodies to Margetuximab (Immunogenicity)(Assessed Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Day 1 of every odd cycle, and end of treatment visit, average 12 months)
- Maximum Concentration of Margetuximab at Steady State(At end of infusion on Cycle 1, Day 1. Cycle 2, Day 1; Cycle 3, Days 1 and 2; Cycle 5 Day 1, Cycle 7 Day 1, and end of treatment visit, average 12 months)
- Progression Free Survival (PFS)(24 Months)
- Change From Baseline in Pharmacodynamic Markers in Whole Blood(from first dose to the end of treatment, average about 12 months)
- Clearance(Predose and at end of infusion on Cycle 1, Days 1, 2 and 8: Cycle 2, Day 1; Cycle 3, Days 1 and 2; Cycle 5 Day 1, Cycle 7 Day 1, and end of treatment visit, average 12 months.)
- Volume of Distribution at Steady State(Predose and at end of infusion on Cycle 1, Days 1, 2 and 8: Cycle 2, Day 1; Cycle 3, Days 1 and 2; Cycle 5 Day 1, Cycle 7 Day 1, and end of treatment visit average 12 months .)
- Analysis of HER2 Tumor Cell Membrane Expression in Biopsy Specimens Before and After Treatment(from first dose to the end of treatment, average 12 months.)
- Area Under the Concentration Time Curve at Steady State (AUC ss)(Predose and at end of infusion on Cycle 1, Days 1, 2 and 8: Cycle 2, Day 1; Cycle 3, Days 1 and 2; Cycle 5 Day 1, Cycle 7 Day 1, and end of treatment visit, average 12 months)