A Phase 1, 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, BAY 2315497 Injection Alone, and in Combination With Darolutamide (BAY 1841788), in Patients With Metastatic Castration Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 63
- 试验地点
- 5
- 主要终点
- Maximum tolerated dose (MTD) of BAY2315497 injection in combination with darolutamide
研究概览
简要总结
The study medication (BAY 2315497 Injection) is a thorium-227 labeled immuno-conjugate, specific for the prostate-specific membrane antigen (PSMA), which will be evaluated in patients with metastatic castration resistant prostate cancer. In this study, this investigational medication will be administered to patients for the first time. The primary objective of the study is to define the safety and tolerability profile and Maximal Tolerated Dose (MTD) of BAY2315497 Injection alone, or in combination with darolutamide. The secondary objectives are to determine the recommended dose for further clinical development of BAY2315497 Injection alone, or in combination with darolutamide and to investigate how the study drug is distributed and cleared from the body.
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
- Male
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
BAY2315497 dose escalation
The thorium-227 dose will be escalated in a step-wise fashion to the MTD, according to a predefined dose escalation scheme. The total antibody dose of 50 mg will be evaluated first; on the basis of emerging clinical data, doses within the range of 20-100 mg may be investigated.
干预措施: BAY2315497 Injection (Drug)
BAY2315497 dose escalation in combination with darolutamide
The thorium-227 dose will be escalated in a step-wise fashion to the MTD, according to a predefined dose escalation scheme. In addition, Darolutamide oral dosing at the approved dose of twice daily 600 mg will be initiated 14 days prior to the first BAY2315497 Injection dose on Day 1 of the first cycle. Daily darolutamide dosing will continue throughout the entire BAY2315497 Injection treatment period until withdrawal criteria from study treatment period are met.
干预措施: BAY2315497 Injection (Drug)
BAY2315497 dose escalation in combination with darolutamide
The thorium-227 dose will be escalated in a step-wise fashion to the MTD, according to a predefined dose escalation scheme. In addition, Darolutamide oral dosing at the approved dose of twice daily 600 mg will be initiated 14 days prior to the first BAY2315497 Injection dose on Day 1 of the first cycle. Daily darolutamide dosing will continue throughout the entire BAY2315497 Injection treatment period until withdrawal criteria from study treatment period are met.
干预措施: Darolutamide(BAY1841788) (Drug)
BAY2315497 dose expansion:Dose regimen 1
The thorium-227 and total antibody doses, as well as the treatment regimen, will be selected for expansion on the basis of the safety, PK and overall benefit risk profile of BAY2315497 Injection, observed in the course of the dose escalation.
干预措施: BAY2315497 Injection (Drug)
BAY2315497 dose expansion:Dose regimen 2
The thorium-227 and total antibody doses, as well as the treatment regimen, will be selected for expansion on the basis of the safety, PK and overall benefit risk profile of BAY2315497 Injection, observed in the course of the dose escalation.
干预措施: BAY2315497 Injection (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) of BAY2315497 injection in combination with darolutamide
时间窗: Cycle 1 (42 days)
The maximum dose at which the incidence of DLTs occurring during Cycle 1 is below 30%.
Maximum tolerated dose (MTD) of BAY2315497 injection
时间窗: Cycle 1 (42 days)
The maximum dose at which the incidence of DLTs occurring during Cycle 1 is below 30%.
次要结局
- Area under the curve from time of dosing to 42 days after dosing [AUC(0-42)] days of thorium of BAY2315497 Injection(Cycle 1 (From day 1 to 43))
- Cmax of radium of BAY2315497 Injection(Cycle 1 (From day 1 to 43))
- Cmax of total antibody of BAY2315497 Injection(Cycle 1 (From day 1 to 43))
- AUC(0-42) days of total antibody of BAY2315497 Injection(Cycle 1 (From day 1 to 43))
- Recommended dose for further clinical development of BAY2315497 injection in combination with darolutamide(Up to 6 cycles (each cycle is 42 days, a maximum of 3 additional treatment cycles may be administered in case a favorable benefit risk profile is documented))
- Cmax of radium of BAY2315497 Injection in combination with darolutamide(Cycle 1 (From day 1 to 43))
- Maximum observed concentration (Cmax) of thorium of BAY2315497 Injection(Cycle 1 (From day 1 to 43))
- AUC(0-42) days of radium of BAY2315497 Injection(Cycle 1 (From day 1 to 43))
- Area under the curve from time of dosing to 42 days after dosing [AUC(0-42)] days of thorium of BAY2315497 Injection in combination with darolutamide(Cycle 1 (From day 1 to 43))
- AUC(0-42) days of radium of BAY2315497 Injection in combination with darolutamide(Cycle 1 (From day 1 to 43))
- Cmax of total antibody of BAY2315497 Injection in combination with darolutamide(Cycle 1 (From day 1 to 43))
- AUC(0-42) days of total antibody of BAY2315497 Injection in combination with darolutamide(Cycle 1 (From day 1 to 43))
- Recommended dose for further clinical development of BAY2315497 injection(Up to 6 cycles (each cycle is 42 days, a maximum of 3 additional treatment cycles may be administered in case a favorable benefit risk profile is documented))
- Maximum observed concentration (Cmax) of thorium of BAY2315497 Injection in combination with darolutamide(Cycle 1 (From day 1 to 43))