An Open-label, First-in-human, Multi-center Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of a Thorium-227 Labeled Antibody-chelator Conjugate, BAY2287411 Injection, in Patients With Solid Tumors Known to Express Mesothelin
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 36
- 试验地点
- 7
- 主要终点
- Proportion of participants with treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), and serious adverse events (SAEs)
研究概览
简要总结
The purpose of this study is to evaluate, in patients with tumors known to express the protein mesothelin, the following properties of BAY2287411 injection:
- safety (to identify, assess, minimize, and appropriately manage the risks associated to the study drug)
- tolerability (the degree to which side effects can be tolerated by your body)
- maximum tolerated dose
- pharmacokinetics (the effect of your body on the study drug)
- anti-tumor activity
- recommended dose for further clinical development
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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 informed consent
- •Male or female subjects ≥ 18 years of age
- •ECOG PS (Eastern Cooperative Oncology Group Performance Status) of 0 or 1
- •Patients with advanced malignant epithelioid mesothelioma or advanced recurrent serous ovarian cancer, who have exhausted available therapeutic options; in addition, in the dose expansion part of the study, patients with metastatic pancreatic adenocarcinoma, who have exhausted available therapeutic options
- •Availability of fresh or archival tumor tissue samples
- •Adequate bone marrow, liver and renal function, as assessed by pre-defined laboratory requirements (within 28 days before start of study drug treatment)
- •A negative serum pregnancy test in women of childbearing potential (WOCBP) performed within 7 days before the start of study drug administration. Women and men of reproductive potential must agree to use highly effective methods of contraception, when sexually active.
排除标准
- •Impaired cardiac function, clinically significant cardiac disease or cardiac arrhythmias
- •Pericarditis (any CTCAE grade) or pericardial effusion (CTCAE Grade ≥ 2)
- •Left Ventricular Ejection Fraction (LVEF) < 50% (as measured at screening by echocardiogram).
- •History of anaphylactic reactions to monoclonal antibody therapy
- •History of Myelodysplastic syndrome (MDS)/treatment-related acute myeloid leukemia (t-AML) or with features suggestive of MDS/AML
- •Infections of CTCAE (Common Terminology Criteria for Adverse Events) version 5.0 Grade 2 not responding to therapy or active clinically serious infections of CTCAE Grade >2; known human immunodeficiency virus (HIV) infection; active hepatitis B virus (HBV) or hepatitis C virus (HCV)infection requiring treatment. Patients with chronic HBV or HCV infection are eligible at the investigator's discretion provided that the disease is stable and sufficiently controlled under treatment
- •Known brain, spinal or meningeal metastases
研究组 & 干预措施
Dose escalation cohort a
Subjects with either advanced recurrent epithelioid mesothelioma or serous ovarian cancer who have exhausted available therapeutic options.
The dose of Thorium-227 will start at 1.5 MBq and increase in steps of 1.0 or 1.5 MBq, with antibody doses of 10 mg.
干预措施: BAY2287411 (Drug)
Dose escalation cohort b
Subjects with either advanced recurrent epithelioid mesothelioma or serous ovarian cancer who have exhausted available therapeutic options.
The dose of Thorium-227 will start at 1.5 MBq and increase in steps of 1.0 or 1.5 MBq, with a total antibody dose within the range of 10 - 50 mg.
干预措施: BAY2287411 (Drug)
Dose Expansion Cohort 1
Subjects with advanced recurrent epithelioid mesothelioma or serous ovarian cancer, who have exhausted available therapeutic options
Dose / Regimen 1 (to be determined after completion of the dose escalation)
干预措施: BAY2287411 (Drug)
Dose Expansion Cohort 2
Subjects with advanced recurrent epithelioid mesothelioma or serous ovarian cancer, who have exhausted available therapeutic options
Dose / Regimen 2 (to be determined after completion of the dose escalation)
干预措施: BAY2287411 (Drug)
Dose expansion Cohort 3 (optional)
Subjects with histologically or cytologically confirmed unresectable, metastatic or locally advanced pancreatic ductal adenocarcinoma
Dose / Regimen to be determined
干预措施: BAY2287411 (Drug)
Dose escalation cohort c
Subjects with either advanced recurrent epithelioid mesothelioma or serous ovarian cancer who have exhausted available therapeutic options.
The dose of Thorium-227 will start at 1.5 MBq and increase in steps of 1.0 or 1.5 MBq, with antibody doses of 10 - 150 mg mg.
干预措施: BAY2287411 (Drug)
Dose escalation cohort d
Subjects with either advanced recurrent epithelioid mesothelioma or serous ovarian cancer who have exhausted available therapeutic options.
The dose of Thorium-227 will start at 1.5 MBq and increase in steps of 1.0 or 1.5 MBq, with antibody doses of 10 - 400 mg.
干预措施: BAY2287411 (Drug)
结局指标
主要结局
Proportion of participants with treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), and serious adverse events (SAEs)
时间窗: 6 months after the end of treatment
Incidence of DLTs (dose-limiting toxicity)
时间窗: 6 weeks (42 days)
次要结局
- Cmax of Thorium-227 after single dose of Cycle 1(From Day 1 to 43)
- AUC(0-42 days) of Total antibody after single dose of Cycle 1(From Day 1 to 43)
- Cmax of Radium-223 after single dose of Cycle 1(From Day 1 to 43)
- Cmax of Total antibody after single dose of Cycle 1(From Day 1 to 43)
- AUC(0-42 days) of Radium-223 after single dose of Cycle 1(From Day 1 to 43)
- AUC(0-42 days) of Thorium-227 after single dose of Cycle 1(From Day 1 to 43)