NCT01148849已完成1 期
A Phase 1, Dose Escalation Study of MGAH22 in Patients With Refractory HER2 Positive Breast Cancer and Patients With Other HER2 Positive Carcinomas for Whom No Standard Therapy Is Available
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- MacroGenics
- 入组人数
- 66
- 试验地点
- 3
- 主要终点
- Occurrence of Adverse Events and Serious Adverse Events
研究概览
简要总结
The purpose of this study is to determine if MGAH22 is safe when given by intravenous (IV) infusion to patients with HER2-positive cancer. The study will also evaluate how long MGAH22 stays in the blood and how long it takes for it to leave the body, what is the highest dose that can safely be given, and whether it has an effect on tumors.
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
- •Histologically or cytologically confirmed carcinoma that overexpresses HER2 by immunohistochemistry (2+ or 3+ positivity by HercepTest or equivalent).
- •Progressive disease during or after last treatment regimen.
- •Appropriate treatment history for histological entity.
- •ECOG Performance Status <=
- •Life expectancy >= 3 month.
- •Measurable disease
- •Acceptable laboratory parameters and adequate organ reserve.
- •Baseline LVEF >50%
排除标准
- •Lifetime anthracycline exposure > 350 mg/m2 of doxorubicin or equivalent
- •Major surgery within four weeks before enrollment.
- •Known hypersensitivity to murine or recombinant proteins, polysorbate 80, or any excipient contained in the drug formulation.
- •Second primary malignancy that has not been in remission for greater than 3 years. Treated non-melanoma skin cancer, cervical carcinoma in situ on biopsy, or squamous intraepithelial lesion on PAP smear, localized prostate cancer (Gleason score < 6), or resected melanoma in situ are exceptions and do not require a 3 year remission.
- •Active viral, bacterial, or systemic fungal infection requiring parenteral treatment within four weeks of enrollment. Patients requiring any oral antiviral, fungal, or bacterial therapy must have completed treatment within one week of enrollment.
- •History of chronic or recurrent infections that require continual use of antiviral, antifungal, or antibacterial agents.
- •History of deep vein thrombosis, pulmonary embolism, myocardial infarction, or stroke within three months of enrollment.
- •Known history of central nervous system (CNS) metastatic disease with evidence of residual or recurrent disease upon entry.
- •New York Heart Association class III or IV heart disease.
研究组 & 干预措施
Cohort 1: 0.1 mg/kg weekly for 4 weeks
Experimental
Anti-HER2 monoclonal antibody (margetuximab)
干预措施: margetuximab (Biological)
Cohort 2: 0.3 mg/kg weekly for 4 weeks
Experimental
Anti-HER2 monoclonal antibody (margetuximab)
干预措施: margetuximab (Biological)
Cohort 3: 1.0 mg/kg weekly for 4 weeks
Experimental
Anti-HER2 monoclonal antibody (margetuximab)
干预措施: margetuximab (Biological)
Cohort 4: 3.0 mg/kg weekly for 4 weeks
Experimental
Anti-HER2 monoclonal antibody (margetuximab)
干预措施: margetuximab (Biological)
Cohort 5: 6.0 mg/kg weekly for 4 weeks
Experimental
Anti-HER2 monoclonal antibody (margetuximab)
干预措施: margetuximab (Biological)
Cohort 6: 10 mg/kg weekly every 3 weeks
Experimental
Anti-HER2 monoclonal antibody (margetuximab)
干预措施: margetuximab (Biological)
Cohort 7: 15 mg/kg weekly every 3 weeks
Experimental
Anti-HER2 monoclonal antibody (margetuximab)
干预措施: margetuximab (Biological)
Cohort 8: 18 mg/kg weekly every 3 weeks
Experimental
Anti-HER2 monoclonal antibody (margetuximab)
干预措施: margetuximab (Biological)
结局指标
主要结局
Occurrence of Adverse Events and Serious Adverse Events
时间窗: Up to 28 days after last infusion
Note that serious adverse events that are considered study drug related can be reported at any time after Study Day 50 or 28 days after the last infusion.
次要结局
- Number of participants with dose limiting toxicities for weekly dosing(up to Study Day 28 for weekly dosing)
- Number of participants with dose limiting toxicities every 3-week dosing(Up to Study Day 21 day for every 3-week dosing)
- Concentration of Margetuximab at Steady State once-weekly doses of margetuximab(Study Day 1, 2, 4, 5, 8, 15, 22, 29 ,36, 50, every 4 weeks thereafter throughout study completion, average 2 months.)
- Number of patients who develop treatment-emergent anti-drug antibodies to margetuximab (Immunogenicity)(Study Day 1, 22, 50, every 4 weeks thereafter throughout study completion, average 2 months.)
- Maximum Concentration of Margetuximab at Steady State once every 3 weeks schedule(Study Day 1, 2, 4, 5, 22, 29 ,36, 50, every 3 weeks thereafter throughout study completion, average 10 months.)
- Area Under the Concentration Time Curve at Steady State (AUC ss) once every 3 weeks schedule(Study Day 1 through Day 22)
- Area Under the Concentration Time Curve at Steady State (AUC ss) weekly dosing schedule(Study Day 1 through Day 8)
- Clearance once every 3 weeks schedule(Study Day 1, 2, 4, 5, 22, 29 ,36, 50, every 3 weeks thereafter through study completion, average 10 months)
- Volume of Distribution at Steady State once every 3 weeks(Study Day 1, 2, 4, 5, 22, 29 ,36, 50, every 3 weeks thereafter through study completion, average 10 months)
- Terminal Half-life once every 3 weeks schedule(Study Day 1 through Day 22)
- Terminal Half-life once every weekly dosing schedule(Study Day 1 through Day 8)
- Number of Patients Who Develop Treatment-emergent Anti-drug Antibodies to Margetuximab once every 3 weeks schedule(Study Day 1, 2, 4, 5, 22, 29 ,36, 50, every 3 weeks thereafter through study completion, average 10 months)
- Number of Patients with a Complete Response (CR) or Partial Response (PR) to Treatment(Assessed at 6, 18, 30, 42, and 54 weeks, they every 24 weeks until treatment discontinuation, average 10 months)
- Duration of response(Assessed at 6, 18, 30, 42, and 54 weeks, they every 24 weeks until treatment discontinuation,average 10 months)
- Progression free survival(Assessed at 6, 18, 30, 42, and 54 weeks, they every 24 weeks until treatment discontinuation, average 10 months)
- Number of patients with complete response, partial response, stable disease, or progressive disease according to each CD16A-158 genotype (FF, FV, VV)(Fc receptor genotypes assessed prior to study treatment. Response to treatment assessed at 6, 18, 30, 42, and 54 weeks, then every 24 weeks until treatment discontinuation, average 10 months)
- Changes in immune cell subsets(Before infusion and 1 hour after infusion on Study Day 1, Study Day 2, before infusion on Study Day 22 and 50)
- Serum cytokines in the blood(Study Day 1, 2, 4, 5, 22, 29 ,36, 50, every 3 weeks thereafter through study completion, average 10 months)
- Amount HER2 in the blood(Before infusion and 1 hour after infusion on Study Day 1, Study Day 2, before infusion on Study Day 22 and 50)
- Antibody dependent cellular cytotoxicity (ADCC) activity(Before infusion and 1 hour after infusion on Study Day 1, Study Day 2, before infusion on Study Day 22 and 50)
- Fc receptor occupancy(Before infusion and 1 hour after infusion on Study Day 1, Study Day 2, before infusion on Study Day 22 and 50)
研究者
研究点 (3)
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