A Phase I, Open-Label, Escalation and Expansion Study to Evaluate Dosimetry, Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of CEA-Pre-Targeted 212Pb Therapy in Participants With Metastatic Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 180
- 试验地点
- 4
- 主要终点
- Part 1 to 3: Percentage of Participants With Adverse Events (AE)
研究概览
简要总结
This study will evaluate the dosimetry, safety, efficacy, pharmacokinetics (PK), pharmacodynamics and immunogenicity of CEA-PRIT 2.0 in participants with metastatic microsatellite-stable (MSS) mCRC who are intolerant to or have progressed after having received available standard-of-care (SOC) therapies.
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
- •Histologically confirmed adenocarcinoma originating from the colon or rectum
- •Metastatic disease (Stage IV American Joint Committee on Cancer, Version 7)
- •Confirmed MSS and/or proficient mismatch repair (MMR) status
- •Experienced disease progression during or within 3 months following the last administration of systemic anti-cancer therapies for metastatic disease
- •Presence of measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •Life expectancy estimated by the Investigator to be >=12 weeks
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1
- •Adequate cardiovascular, hematological and renal function and laboratory parameters
排除标准
- •Pregnant or breastfeeding or intending to become pregnant
- •Participants with active central nervous system (CNS) metastases
- •History of malignancy other than the one under investigation
- •Any unresolved toxicities from prior therapy, i.e., radiotherapy, chemotherapy, targeted therapy or surgical procedure
- •Major surgery or significant traumatic injury <4 weeks prior to the first CEA-PRIT 2.0 administration (excluding biopsies) or anticipation of the need for major surgery during study treatment
- •Participants have a known confirmed positive test for HIV
- •Positive hepatitis B surface antigen (HBsAg) test, and/or positive total hepatitis B core Ab (HBcAb) test at screening.
- •Positive hepatitis C (HCV) Ab test result at screening
- •Any anticancer treatment or any investigational agent within 4 weeks (or 5 times the half-life, whichever is shorter) prior to C1D1
- •Prior treatment with a CEA-targeted agent or systemic radio therapy
研究组 & 干预措施
Part 2 (212Pb-DOTAM Administered Activity Escalation)
Participants will receive SPLIT Abs at the dose and dosing interval selected in Part 1 in combination with 212Pb-DOTAM. The administered activity of 212Pb-DOTAM will be increased stepwise in each cohort to identify the maximum tolerated administered 212 activity (MTA) or a recommended Phase 2 administered activity (RP2A).
干预措施: 203Pb-DOTAM (Drug)
Part 1 (Dosimetry)
Participants will receive SeParated v-domains LInkage Technology Antibodies (SPLIT Abs) administered intravenously (IV). During Cycle 1, following an initial dosing interval, participants will receive 203Pb-DOTAM for imaging-based dosimetry assessment, followed by administration of 212Pb-DOTAM.
In other cycles, participants will receive SPLIT Abs in combination with 212Pb-DOTAM only. Treatment will be administered every 4 weeks (Q4W) for up to 6 cycles. Each cycle is 28 days.
干预措施: SPLIT Abs (Drug)
Part 3 (Expansion)
Participants will receive SPLIT Abs in combination with 212Pb-DOTAM at the RP2A identified based on results from Parts 1 and 2.
干预措施: SPLIT Abs (Drug)
Part 1 (Dosimetry)
Participants will receive SeParated v-domains LInkage Technology Antibodies (SPLIT Abs) administered intravenously (IV). During Cycle 1, following an initial dosing interval, participants will receive 203Pb-DOTAM for imaging-based dosimetry assessment, followed by administration of 212Pb-DOTAM.
In other cycles, participants will receive SPLIT Abs in combination with 212Pb-DOTAM only. Treatment will be administered every 4 weeks (Q4W) for up to 6 cycles. Each cycle is 28 days.
干预措施: 203Pb-DOTAM (Drug)
Part 1 (Dosimetry)
Participants will receive SeParated v-domains LInkage Technology Antibodies (SPLIT Abs) administered intravenously (IV). During Cycle 1, following an initial dosing interval, participants will receive 203Pb-DOTAM for imaging-based dosimetry assessment, followed by administration of 212Pb-DOTAM.
In other cycles, participants will receive SPLIT Abs in combination with 212Pb-DOTAM only. Treatment will be administered every 4 weeks (Q4W) for up to 6 cycles. Each cycle is 28 days.
干预措施: 212Pb-DOTAM (Drug)
Part 2 (212Pb-DOTAM Administered Activity Escalation)
Participants will receive SPLIT Abs at the dose and dosing interval selected in Part 1 in combination with 212Pb-DOTAM. The administered activity of 212Pb-DOTAM will be increased stepwise in each cohort to identify the maximum tolerated administered 212 activity (MTA) or a recommended Phase 2 administered activity (RP2A).
干预措施: SPLIT Abs (Drug)
Part 2 (212Pb-DOTAM Administered Activity Escalation)
Participants will receive SPLIT Abs at the dose and dosing interval selected in Part 1 in combination with 212Pb-DOTAM. The administered activity of 212Pb-DOTAM will be increased stepwise in each cohort to identify the maximum tolerated administered 212 activity (MTA) or a recommended Phase 2 administered activity (RP2A).
干预措施: 212Pb-DOTAM (Drug)
Part 3 (Expansion)
Participants will receive SPLIT Abs in combination with 212Pb-DOTAM at the RP2A identified based on results from Parts 1 and 2.
干预措施: 212Pb-DOTAM (Drug)
结局指标
主要结局
Part 1 to 3: Percentage of Participants With Adverse Events (AE)
时间窗: Up to approximately 5 years
Part 1: Serum Concentration of SPLIT Abs
时间窗: Up to approximately 48 weeks
Part 1: Time Course of Blood, Plasma, and Urine Radioactivity for 203Pb-DOTAM
时间窗: Up to approximately 48 weeks
Part 1 to 2: Absorbed Radiation Dose of 212Pb-DOTAM extrapolated from 203Pb-DOTAM
时间窗: Up to approximately 48 weeks
次要结局
- Part 1 to 3: Percentage of Participants With Anti-Drug Antibodies (ADAs) Against SPLIT Abs(Baseline, Up to approximately 48 weeks)
- Part 1 to 3: Objective Response Rate (ORR)(Up to approximately 48 weeks)
- Part 1 to 3: Disease Control Rate (DCR)(Up to approximately 48 weeks)
- Part 1 to 3: Duration of Response (DOR)(Up to approximately 48 weeks)
- Part 1 to 3: Progression-Free Survival (PFS)(Up to approximately 48 weeks)
- Part 1 to 3: Overall Survival (OS)(Up to approximately 48 weeks)
- Part 1 to 3: Correlation Between Carcinoembryogenic Antigen (CEA) Tumor Expression and Clinical Activity(Up to approximately 48 weeks)
- Part 1 to 2: Uptake of 203Pb-DOTAM in Tumor and Normal Tissue(Up to approximately 48 weeks)
- Part 1 to 2: Time Course of Blood, Plasma, and Urine Radioactivity for 203Pb-DOTAM(Up to approximately 48 weeks)
- Part 1 to 3: Serum Concentration of CEA-PRIT 2.0(Up to approximately 48 weeks)
- Part 1 to 3: Time Course of Blood and Plasma Radioactivity for 212Pb-DOTAM(Up to approximately 48 weeks)