A Phase 1/2 First-in-Human Study of the Safety and Efficacy of IMC-R117C (PIWIL1 × CD3 ImmTAC® Bispecific Protein) as a Single Agent and in Combination in HLA-A*02:01-Positive Participants With Selected Advanced PIWIL1-Positive Cancers
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 600
- 试验地点
- 15
- 主要终点
- Dose Escalation: Percentage of participants with ≥1 dose-limiting toxicity (DLT)
研究概览
简要总结
This phase 1/2 first-in-human study is designed to test the safety and efficacy of IMC-R117C (PIWIL1 × CD3 ImmTAC® Bispecific Protein) as a single agent and in combination with other therapies in HLA-A*02:01-positive participants with selected advanced PIWIL1-Positive cancers.
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
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- •HLA-A*02:01-positive
- •Histologically confirmed advanced colorectal, esophageal, gastric, or ovarian carcinoma
- •Archived or fresh tumor tissue sample that must be confirmed as adequate
- •Evaluable/Measurable disease per RECIST 1.1
- •Previously received applicable standard treatments
- •Male and female participants of childbearing potential who are sexually active with a non-sterilized partner must agree to use highly effective methods of birth control
排除标准
- •Symptomatic or untreated central nervous system metastasis
- •Recent bowel obstruction
- •Ongoing ascites or effusion requiring recent drainages
- •Significant ongoing toxicity from prior anticancer treatment
- •Out-of-range laboratory values
- •Clinically significant lung, heart, or autoimmune disease
- •Ongoing requirement for immunosuppressive treatment
- •Significant secondary malignancy
- •Hypersensitivity to study drug or excipients
- •Pregnant or lactating
研究组 & 干预措施
Arm A: IMC-R117C Monotherapy Dose-Escalation
Participants receive IMC-R117C intravenous (IV) infusion.
干预措施: IMC-R117C (Drug)
Arm B: IMC-R117C Combination Dose-Escalation
Participants receive IMC-R117C IV infusion in combination with standard of care chemotherapy and antiangiogenic agent
干预措施: IMC-R117C (Drug)
Arm B: IMC-R117C Combination Dose-Escalation
Participants receive IMC-R117C IV infusion in combination with standard of care chemotherapy and antiangiogenic agent
干预措施: Chemotherapy drug (Drug)
Arm B: IMC-R117C Combination Dose-Escalation
Participants receive IMC-R117C IV infusion in combination with standard of care chemotherapy and antiangiogenic agent
干预措施: Antiangiogenic Agent (Drug)
Arm C: IMC-R117C Combination Dose-Escalation
Participants receive IMC-R117C IV infusion with targeted therapies
干预措施: IMC-R117C (Drug)
Arm C: IMC-R117C Combination Dose-Escalation
Participants receive IMC-R117C IV infusion with targeted therapies
干预措施: Kinase inhibitor (Drug)
Arm C: IMC-R117C Combination Dose-Escalation
Participants receive IMC-R117C IV infusion with targeted therapies
干预措施: Monoclonal antibody (Drug)
Arm D: Control Arm
Participants receive standard of care chemotherapy and antiangiogenic agent
干预措施: Chemotherapy drug (Drug)
Arm D: Control Arm
Participants receive standard of care chemotherapy and antiangiogenic agent
干预措施: Antiangiogenic Agent (Drug)
结局指标
主要结局
Dose Escalation: Percentage of participants with ≥1 dose-limiting toxicity (DLT)
时间窗: Up to ~24 months
Dose Escalation: Percentage of participants with ≥1 adverse event (AE)
时间窗: Up to ~24 months
Dose Escalation: Percentage of participants with ≥1 serious adverse event (SAE)
时间窗: Up to ~24 months
Dose Escalation: Percentage of participants with significant changes in electrocardiogram (ECG) recordings
时间窗: Up to ~24 months
Dose Escalation: Percentage of participants with significant changes in vital signs
时间窗: Up to ~24 months
Dose Escalation: Percentage of participants with significant changes in laboratory results
时间窗: Up to ~24 months
Dose Escalation: Percentage of participants with a dose interruption, reduction, or discontinuation
时间窗: Up to ~24 months
Expansion: Best Overall Response (BOR) as Determined by RECIST v1.1
时间窗: Up to ~24 months
次要结局
- Dose Escalation: Best Overall Response (BOR) as Determined by RECIST v1.1 with IMC-R117C Monotherapy and in Combination(Up to ~36 months)
- Dose Escalation: Duration of Response (DOR) as Determined by RECIST v1.1 with IMC-R117C Monotherapy and in Combination(Up to ~36 months)
- Dose Escalation: Progression-free survival (PFS) as Determined by RECIST v1.1 with IMC-R117C Monotherapy and in Combination(Up to ~36 months)
- Dose Escalation: Overall Survival (OS) with IMC-R117C Monotherapy and in Combination(Up to ~36 months)
- Expansion: Duration of Response (DOR) as Determined by RECIST v1.1 with IMC-R117C Monotherapy(Up to ~36 months)
- Expansion: Progression-free survival (PFS) as Determined by RECIST v1.1 with IMC-R117C Monotherapy(Up to ~36 months)
- Expansion: Overall Survival (OS) with IMC-R117C Monotherapy(Up to ~36 months)
- Expansion: Percentage of participants with ≥1 Serious Adverse Events (SAE)(Up to ~24 months)
- Expansion: Percentage of participants with significant changes in electrocardiogram (ECG) recordings(Up to ~24 months)
- Expansion: Percentage of participants with ≥1 Adverse Events (AE)(Up to ~24 months)
- Expansion: Percentage of participants with significant changes in vital signs(Up to ~24 months)
- Expansion: Percentage of participants with significant changes in laboratory findings(Up to ~24 months)
- Expansion: Percentage of participants with dose interruptions, reductions, or discontinuation(Up to ~24 months)
- All Study: Plasma Concentration of IMC-R117C(Up to ~36 months)
- All Study: Incidence of anti-IMC-R117C Antibody Formation(Up to ~36 months)
- All Study: Incidence of tumor expression and localization of PIWIL1(Up to ~36 months)