A Phase I/II First-In-Human Clinical Trial to Evaluate the Safety, Tolerability and Anti-Tumor Activity of IMA402, a Bispecific T Cell-Engaging Receptor Molecule (TCER®) Targeting PRAME, as Monotherapy or in Combination With a Checkpoint Inhibitor in Patients With Recurrent and/or Refractory Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 400
- 试验地点
- 57
- 主要终点
- Phase I/II: Number of patients with serious TEAEs
研究概览
简要总结
The goal of this clinical trial is to evaluate the safety, tolerability and anti-tumor activity of IMA402 in patients with recurrent and/or refractory solid tumors.
Primary objectives:
- To determine the maximum tolerated doses and/or recommended doses for extensions for IMA402 as monotherapy and in combination with pembrolizumab (Phase Ia)
- To characterize the safety and tolerability of IMA402 as monotherapy and in combination (Phase I/II)
- To evaluate anti-tumor activity of IMA402 as monotherapy and in combination (Phase II)
Secondary objectives:
- To evaluate the initial anti-tumor activity of IMA402 as monotherapy and in combination (Phase I)
- To evaluate anti-tumor activity of IMA402 as monotherapy and in combination (Phase II)
- To describe the PK of IMA402 as monotherapy and in combination (Phase I/II)
详细描述
The study will be conducted in two phases:
- Phase Ia: Dose escalation/de-escalation
- Phase Ib: Dose extension
- Phase II: Dose extension in selected Indication-specific extension cohort(s) (ISEC)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Patients ≥ 18 years old
- •Patients must have a specific pathologically confirmed and documented advanced and/or metastatic solid tumor indication
- •Patients must have received or not be eligible for indicated standard-of-care treatments per cohort
- •Measurable disease according to RECIST 1.1
- •Confirmed HLA status
- •ECOG Performance Status of 0 to 1
- •Adequate baseline hematologic, hepatic and renal function, acceptable coagulation status
排除标准
- •Other active malignancies that require treatment or that might interfere with the trial endpoints
- •The patient is pregnant or is breastfeeding
- •History of hypersensitivity to components of IMA402 or rescue medications; hypersensitivity to or contraindication according to current SmPC for respective combination medicinal product
- •The patient has concurrent severe and/or uncontrolled medical disease. Any other health condition that would, in the investigator's or sponsor's judgement, contraindicate the patient's participation in the clinical trial because of safety concerns or compliance with clinical trial procedures
- •Patients with active brain metastases, history of bleeding into brain metastases, known brain metastases who are receiving therapeutic anticoagulation
研究组 & 干预措施
Dose escalation/de-escalation (Phase Ia)
Dose-Finding of IMA402 as monotherapy or in combination with checkpoint inhibitor (Phase Ia)
干预措施: IMA402 and checkpoint inhibitor (Drug)
Dose extension (Phase Ib)
Extension cohorts of IMA402 as monotherapy or in combination based on maximum tolerated dose (MTD) and/or recommended doses for extensions (RDEs) (Phase Ib)
干预措施: IMA402 and checkpoint inhibitor (Drug)
Dose extension (Phase Ib)
Extension cohorts of IMA402 as monotherapy or in combination based on maximum tolerated dose (MTD) and/or recommended doses for extensions (RDEs) (Phase Ib)
干预措施: IMA402 and chemotherapy (Drug)
Dose extension (Phase Ib)
Extension cohorts of IMA402 as monotherapy or in combination based on maximum tolerated dose (MTD) and/or recommended doses for extensions (RDEs) (Phase Ib)
干预措施: IMA402 and IMA401 (Drug)
Dose extension (Phase Ib)
Extension cohorts of IMA402 as monotherapy or in combination based on maximum tolerated dose (MTD) and/or recommended doses for extensions (RDEs) (Phase Ib)
干预措施: IMA402 and monoclonal antibody (Drug)
Dose extension (Phase Ib)
Extension cohorts of IMA402 as monotherapy or in combination based on maximum tolerated dose (MTD) and/or recommended doses for extensions (RDEs) (Phase Ib)
干预措施: IMA402 and chemotherapy +/- monoclonal antibody (Drug)
Dose extension (Phase II)
Selected ISEC investigated on MTD/RDEs based on a manageable/favorable safety profile and initial signs of anti-tumor activity (Phase II)
干预措施: IMA402 and checkpoint inhibitor (Drug)
Dose extension (Phase II)
Selected ISEC investigated on MTD/RDEs based on a manageable/favorable safety profile and initial signs of anti-tumor activity (Phase II)
干预措施: IMA402 (Drug)
Dose extension (Phase Ib)
Extension cohorts of IMA402 as monotherapy or in combination based on maximum tolerated dose (MTD) and/or recommended doses for extensions (RDEs) (Phase Ib)
干预措施: IMA402 (Drug)
Dose escalation/de-escalation (Phase Ia)
Dose-Finding of IMA402 as monotherapy or in combination with checkpoint inhibitor (Phase Ia)
干预措施: IMA402 (Drug)
结局指标
主要结局
Phase I/II: Number of patients with serious TEAEs
时间窗: 40 months
Phase I/II: Frequency of dose interruptions and reductions, permanent discontinuations
时间窗: 40 months
Phase I/II: Number of patients with treatment-emergent adverse events (TEAEs)
时间窗: 40 months
Phase I/II: Duration of dose interruptions and reductions, permanent discontinuations
时间窗: 40 months
Phase II: Overall response rate (ORR) based on best overall response (BOR) of complete response (CR) and partial response (PR) locally assessed using Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1)
时间窗: 40 months
Phase I: Number of patients with dose limiting toxicities (DLTs)
时间窗: 24 months
次要结局
- Phase II: ORR based on BOR of CR and PR locally assessed using iRECIST(40 months)
- Phase I/II: Determination of PK parameter: half-life (t1/2)(40 months)
- Phase I/II: Determination of PK parameter: area under the curve (AUC)(40 months)
- Phase I/II: Determination of PK parameter: maximal serum concentration (Cmax)(40 months)
- Phase I/II: Duration of response (DOR) of CR or PR based on RECIST v1.1 and iRECIST(40 months)
- Phase I/II: Progression-free survival (PFS) based on RECIST v1.1 and iRECIST(40 months)
- Phase I/II: Overall survival (OS)(40 months)
- Phase I/II: Determination of PK parameter: minimal serum concentration (Cmin)(40 months)
- Phase I/II: Disease control rate (DCR) of CR, PR or stable disease (SD) (lasting 6 or more weeks) following the initiation of IMA402 based on RECIST v1.1 and iRECIST(40 months)
- Phase I: ORR based on BOR of CR and PR locally assessed using RECIST v1.1 and iRECIST(37 months)