A First-in-human Dose Escalation and Dose Finding Phase 1 Trial of IMAB027 in Patients With Recurrent Advanced Ovarian Cancer (OVAR)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 9
- 主要终点
- Safety and tolerability
研究概览
简要总结
Advanced ovarian cancer is a high medical need indication. Cure is not available to these patients and treatment has palliative intent. A proportion of advanced stage ovarian cancer expresses substantial levels of Claudin 6 (CLDN6), a carcino-embryonic transmembrane protein, which is absent from normal adult human tissue. IMAB027 is a monoclonal antibody that binds to CLDN6. Preclinically IMAB027 was shown to inhibit tumor growth and to kill cancer cells by antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. This trial is a first-in-human dose escalation and dose finding Phase 1 trial of IMAB027 in patients with recurrent advanced ovarian cancer to assess the safety and tolerability, the pharmacokinetics, the antitumoral activity and the immunogenicity of IMAB027.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- Female
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent
- •Female patients ≥18 years of age, no upper age limit
- •Histologically or cytologically confirmed CLDN6+ ovarian cancer of any histology type including primary peritoneal or fallopian tube tumors (histological documentation of the original primary tumor is required via a pathology report)
- •Performance status ECOG 0-2
- •Patients with measurable, non-measurable, or evaluable disease: Evaluable disease: defined as a confirmed CA-125 ≥2 x ULN, Measurable disease (RECIST 1.1): defined as at least one lesion that can be accurately measured in at least one dimension
- •Availability of a FFPE tumor tissue sample or tumor cell positive paracentesis fluid samples (abdominal or pleural cavity) for the assessment of CLDN6 positivity
- •Life expectancy of >12 weeks
- •Adequate organ function defined as:
- •Adequate hematologic function (ANC ≥1000/μl, platelets ≥100.000/μl, hemoglobin ≥9.0 g/dl (can be post transfusion)); Adequate renal function (serum creatinine ≤1.5 mg/dl [114.5 μmol/l] or creatinine clearance rate ≥30 ml/min); Adequate liver function (serum total bilirubin ≤2 x ULN, AST/ALT ≤3 x ULN)
- •Patients of child-bearing potential must have a negative β-HCG urine test within 72 hours before receiving treatment
排除标准
- •Patient is pregnant or breast-feeding
- •Prior allergic reaction or intolerance to a monoclonal antibody (humanized or chimeric)
- •Any prior anti-tumor therapy within 14 days prior to the start of IMAB027 treatment
- •Other concurrent anticancer therapies
- •HIV infection in medical history or active Hepatitis B or C infection requiring treatment
- •History of any one or more of the following cardiovascular conditions within the past 6 months: Myocardial infarction (T-Wave/Non-T-Wave), Unstable angina pectoris Class II, III or IV congestive heart failure as defined by the New York Heart Association (NYHA), History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT). Patients with recent DVT who have been or are treated with therapeutic anti-coagulant agents (excluding warfarin) for at least 6 weeks are eligible
- •Other investigational agents or devices concurrently or within 14 days before start of IMAB027 treatment
- •Any hemoptysis or bleeding event that is clinically relevant within 2 weeks of first dose of study drug
- •Clinical symptoms of brain metastases or tumor-associated spinal cord compression
- •Need for continuous, systemic immunosuppressive therapy
- •Any other medical condition that would, in the opinion of the Investigator, limit the patient's ability to complete the study
研究组 & 干预措施
IMAB027 administration
Monotherapy - different dose Levels.
干预措施: IMAB027 (Drug)
结局指标
主要结局
Safety and tolerability
时间窗: 24 month
Safety profile including type, frequency, severity, relationship of adverse events to investigational medicinal product, dose limiting toxicities, maximum tolerated dose
次要结局
- to assess antitumoral activity(up to 3 years)
- to assess immunogenicity(24 month)
- to assess pharmacokinetics(24 month)