A Multicenter, Open Label, Non-randomized First-in-human Phase 1 Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of BAY 3547926 Alone, and in Combination, in Participants With Advanced Hepatocellular Carcinoma (HCC)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 148
- 试验地点
- 36
- 主要终点
- Part 2 (dose expansion): DCR using RECIST 1.1 by investigator assessment
研究概览
简要总结
In this study, researchers want to learn about the safety of a new drug, BAY 3547926, and how well the drug works in people with a type of liver cancer called advanced hepatocellular carcinoma (HCC), which has a special protein called Glypican 3 (GPC3). Researchers want to find the best dose of BAY 3547926 for people with advanced HCC and look at the way the body absorbs and distributes the drug.
The study drug, BAY 3547926, delivers a radioactive agent to cancer cells. The radioactive agent emits radiations which can damage the cancer cells and cause them to die. These radiations travel a small distance, so are expected to cause little damage to surrounding healthy tissues. This is the first study of BAY 3547926 in humans.
Participants will take part in one of the 4 different parts of the study. In Part 1, participants will receive different doses of BAY 3547926 alone to find the dose that is deemed safe and works best for the participants. When this dose has been found, a larger number of participants will receive BAY 3547926 alone in Part 2 or with other treatments in Parts 3 and 4 of the study.
During the study, the doctors and their study team will do health check-ups, take pictures (scans) of the body, collect blood and urine samples, and ask participants questions about how they are feeling and what health problems they are having.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 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
- •Locally advanced or metastatic and/or unresectable HCC (hepatocellular carcinoma) with histological or cytological confirmation, or non-invasive diagnosis as per American Association for the Study of Liver Diseases (AASLD) criteria in participants with a confirmed diagnosis of cirrhosis.
- •Demonstrated positive centrally confirmed GPC3 expression by immunohistochemistry (IHC) on tumor sample.
- •Disease not amenable to, or progressive disease after, curative surgery and/or locoregional therapies of established efficacy such as resection, local ablation, chemoembolization.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or
- •At least one measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.
- •as assessed by local site Investigator within 28 days prior to the start of the study treatment.
- •Adequate bone marrow and organ function
排除标准
- •Fibrolamellar HCC, sarcomatoid HCC, and mixed hepatocellular/cholangiocarcinoma subtypes.
- •Participants with a history or clinical evidence of CNS metastases, unless they meet specific criteria
- •History of encephalopathy ≥ Grade 2 within the past 12 months
- •Clinically significant ascites
研究组 & 干预措施
BAY 3547926
actinium-225 labeled antibody conjugate
干预措施: BAY 3547922 (Drug)
BAY 3547926
actinium-225 labeled antibody conjugate
干预措施: BAY 3547926 (Drug)
BAY 3547926
actinium-225 labeled antibody conjugate
干预措施: BAY 3713391 (Drug)
BAY 3547926
actinium-225 labeled antibody conjugate
干预措施: BAY 3713389 (Drug)
结局指标
主要结局
Part 2 (dose expansion): DCR using RECIST 1.1 by investigator assessment
时间窗: up to 60 months after first administration
DCR=Disease control rate RECIST=Response Evaluation Criteria in Solid Tumors
Part 2 (dose expansion): DoR using RECIST 1.1 by investigator assessment
时间窗: up to 60 months after first administration
DoR=Duration of response RECIST=Response Evaluation Criteria in Solid Tumors
Part 1 (dose escalation): Occurrence and severity of TEAEs
时间窗: up to 60 months after first administration
TEAE=Treatment emergent adverse event
Part 2 (dose expansion): PFS using RECIST 1.1 by investigator assessment
时间窗: up to 60 months after first administration
PFS=Progression free survival RECIST=Response Evaluation Criteria in Solid Tumors
Part 3 (dose expansion in combination): Occurrence and severity of TEAEs
时间窗: up to 60 months after first administration
TEAE=Treatment emergent adverse event
Part 3 (dose expansion in combination): ORR using RECIST 1.1 by investigator assessment
时间窗: up to 60 months after first administration
ORR= Objective response rate
Part 3 (dose expansion in combination): DCR using RECIST 1.1 by investigator assessment
时间窗: up to 60 months after first administration
DCR=Disease control rate
Part 3 (dose expansion in combination): DoR using RECIST 1.1 by investigator assessment
时间窗: up to 60 months after first administration
DoR=Duration of response
Part 3 (dose expansion in combination): PFS using RECIST 1.1 by investigator assessment
时间窗: up to 60 months after first administration
PFS=Progression free survivial
Part 1 (dose escalation): Recommended safe and active dose (RSAD)
时间窗: up to 60 months after first administration
The RSAD is based on incidence of DLT and preliminary anti-tumor activity (ORR using RECIST 1.1 by Investigator assessment) informed by TITE-CRM. RSAD=Recommended safe and active dose DLT=Dose limiting toxicity ORR=Objective reponse rate RECIST=Response Evaluation Criteria in Solid Tumors TITE-CRM =Time-to-event continual reassessment method
Part 2 (dose expansion): Occurrence and severity of TEAEs
时间窗: up to 60 months after first administration
TEAE=Treatment emergent adverse event
Part 2 (dose expansion): ORR using RECIST 1.1 by investigator assessment
时间窗: up to 60 months after first administration
ORR=Objective reponse rate RECIST=Response Evaluation Criteria in Solid Tumors
Parts 3 and 4 (dose expansion in combination): Occurrence and severity of TEAEs
时间窗: up to 60 months after first administration
TEAE=Treatment emergent adverse event
Parts 3 and 4 (dose expansion in combination): ORR using RECIST 1.1 by investigator assessment
时间窗: up to 60 months after first administration
ORR= Objective response rate
Parts 3 and 4 (dose expansion in combination): DCR using RECIST 1.1 by investigator assessment
时间窗: up to 60 months after first administration
DCR=Disease control rate
Parts 3 and 4 (dose expansion in combination): DoR using RECIST 1.1 by investigator assessment
时间窗: up to 60 months after first administration
DoR=Duration of response
Parts 3 and 4 (dose expansion in combination): PFS using RECIST 1.1 by investigator assessment
时间窗: up to 60 months after first administration
PFS=Progression free survivial
次要结局
- Parts 3 and 4 (dose expansion in combination): Recommended dose level(s) of BAY 3547926 based on clinical data including, but not limited to, occurrence and severity of TEAEs and DLTs, PK and IG(up to 60 months after first administration)
- Parts 3 and 4 (dose expansion in combination): Recommended dosing regimen of BAY 3547926 based on clinical data including, but not limited to, occurrence and severity of TEAEs and DLTs, PK and IG(up to 60 months after first administration)
- Parts 3 and 4 (dose expansion in combination): Recommended schedule of BAY 3547926 based on severity of TEAEs, PK, IG(up to 60 months after first administration)
- Parts 3 and 4 (dose expansion in combination): Cmax of BAY 3547926 after a single dose and after multiple doses of BAY 3547926 in combination(up to 60 months after first administration)
- Parts 3 and 4 (dose expansion in combination): AUC of BAY 3547926 after single dose and after multiple doses of BAY 3547926 in combination(up to 60 months after first administration)
- Parts 3 and 4 (dose expansion in combination): Clearance of BAY 3547926 after single dose and after multiple doses of BAY 3547926 in combination, where applicable and if data allow(up to 60 months after first administration)
- Part 1 (dose escalation): Recommended dose level(s) based on occurrence and severity of TEAEs and DLTs, PK, immunogenicity, and preliminary anit-tumor activity (ORR using RECIST 1.1 by Investigator assessment)(up to 60 months after first administration)
- Part 1 (dose escalation): Recommended dosing regimen based on occurrence and severity of TEAEs and DLTs, PK, immunogenicity, and preliminary anti-tumor activity (ORR using RECIST 1.1 by Investigator assessment)(up to 60 months after first administration)
- Part 1 (dose escalation): ORR using RECIST 1.1 by investigator assessment(up to 60 months after first administration)
- Part 1 (dose escalation): DCR using RECIST 1.1 by investigator assessment(up to 60 months after first administration)
- Part 1 (dose escalation): DoR using RECIST 1.1 by investigator assessment(Up to 60 months after first administration)
- Part 1 (dose escalation): PFS using RECIST 1.1 by investigator assessment(up to 60 months after first administration)
- Part 1 (dose escalation): Cmax of BAY 3547926 after a single dose and after multiple doses(up to 36 weeks after first administration)
- Part 1 (dose escalation): AUC of BAY 3547926 after a single dose and after multiple doses(up to 36 weeks after first administration)
- Part 1 (dose escalation): Clearance of BAY 3547926 after a single dose and after multiple doses if data allow(up to 36 weeks after first administration)
- Part 2 (dose expansion): Recommended dose based on safety, PK, IG and markers of pharmacodynamic activity and efficacy assessments(up to 36 months after first administration)
- Part 2 (dose expansion): Recommended schedule based on safety, PK, IG and markers of pharmacodynamic activity and efficacy assessments(up to 36 months after first administration)
- Part 2 (dose expansion): Cmax of BAY 3547926 after a single dose and after multiple doses(up to 36 weeks after first administration)
- Part 2 (dose expansion): AUC of BAY 3547926 after a single dose and after multiple doses(up to 36 weeks after first administration)
- Part 2 (dose expansion): Clearance of BAY 3547926 after single dose and after multiple doses, where applicable and if data allow(up to 36 weeks after first administration)
- Part 3 (dose expansion in combination): Recommended dose level(s) of BAY 3547926 based on clinical data including, but not limited to, occurrence and severity of TEAEs and DLTs, PK and IG(up to 60 months after first administration)
- Part 3 (dose expansion in combination): Recommended dosing regimen of BAY 3547926 based on clinical data including, but not limited to, occurrence and severity of TEAEs and DLTs, PK and IG(up to 60 months after first administration)
- Part 3 (dose expansion in combination): Recommended schedule of BAY 3547926 based on severity of TEAEs, PK, IG(up to 60 months after first administration)
- Part 3 (dose expansion in combination): Cmax of BAY 3547926 after a single dose and after multiple doses of BAY 3547926 in combination(up to 60 months after first administration)
- Part 3 (dose expansion in combination): AUC of BAY 3547926 after single dose and after multiple doses of BAY 3547926 in combination(up to 60 months after first administration)
- Part 3 (dose expansion in combination): Clearance of BAY 3547926 after single dose and after multiple doses of BAY 3547926 in combination, where applicable and if data allow(up to 60 months after first administration)