A First-in-human, Open-label Trial to Evaluate the Combination of ACTengine® IMA203 With mRNA-4203 in Previously Treated, Unresectable or Metastatic Cutaneous Melanoma or Synovial Sarcoma Patients (ACTengine® IMA203-102)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 15
- 试验地点
- 6
- 主要终点
- Number of participants with dose-limiting toxicities (DLTs)
研究概览
简要总结
This purpose of this clinical trial is to evaluate the safety, tolerability and anti-tumor activity of IMA203 in combination with different doses of mRNA-4203. The trial includes participants with previously treated unresectable or metastatic cutaneous melanoma (CM) or synovial sarcoma (SS).
详细描述
This clinical trial is a multi-center, open-label, non-comparative Phase 1 a/b trial to assess the safety, tolerability, and anti-tumor activity of the combination of IMA203 and mRNA-4203 in HLA-A*02:01 positive patients with previously treated, unresectable or metastatic cutaneous melanoma (CM) and synovial sarcoma (SS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Pathologically confirmed and documented cutaneous melanoma (CM) or synovial sarcoma (SS) with unresectable or metastatic disease
- •HLA-A*02:01 positive
- •Adequate selected organ function per protocol
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
- •Life expectancy more than 5 months
- •CM participants who must have disease progression (resistance, toxicity) on or after at least one PD-1 inhibitor
- •SS participants must have received (or declined) at least one line of treatment (including SoC) and are still in need of further systemic therapy.
- •Female participants of childbearing potential must use adequate contraception prior to trial entry until 12 months after the infusion of IMA203 and 15 days after the last mRNA 4203 dose administration
- •Other protocol defined inclusion criteria could apply
排除标准
- •History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 3 years
- •Pregnant or breastfeeding
- •Serious autoimmune disease
- •History of cardiac conditions as per protocol
- •Prior allogenic stem cell transplantation or solid organ transplantation
- •Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study
- •History of hypersensitivity to cyclophosphamide, fludarabine, or IL-2
- •History of hypersensitivity to mRNA-based medicines
- •Positive for HIV infection or with active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection
- •Any condition contraindicating leukapheresis
- •Participants with lactate dehydrogenase (LDH) greater than threshold allowed per protocol
- •Participants with active brain metastases prior to lymphodepletion
- •Concurrent treatment in another clinical trial or a device trial that could interfere with the IMA203 treatment
- •Participants with renal impairment AND reduced bone marrow reserve per protocol
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
IMA203 with mRNA-4203 in participants with metastatic cutaneous melanoma or synovial sarcoma
This is a non-comparative, open-label trial with different cohorts investigating IMA203 in combination with mRNA-4203.
干预措施: IMA203 (Biological)
IMA203 with mRNA-4203 in participants with metastatic cutaneous melanoma or synovial sarcoma
This is a non-comparative, open-label trial with different cohorts investigating IMA203 in combination with mRNA-4203.
干预措施: mRNA-4203 (Biological)
结局指标
主要结局
Number of participants with dose-limiting toxicities (DLTs)
时间窗: one year post infusion of IMA203
Number of DLTs will be used to determine the maximum tolerated dose (MTD) and/or recommended dose for extension (RDE) after treatment with IMA203 product in combination with mRNA-4203
Number of treatment emergent adverse events (AEs), AEs of special interest, serious AEs (SAEs), changes in laboratory parameters and vital signs, and frequency of dose interruptions, reductions and discontinuations
时间窗: one year post infusion of IMA203
Used to evaluate safety and tolerability of treatment with IMA203 in combination with mRNA-4203
次要结局
- Duration of response (DOR)(one year post infusion of IMA203)
- Disease control rate (DCR)(one year post infusion of IMA203)
- Progression-free survival (PFS)(one year post infusion of IMA203)
- Concentration of IMA203 transgene in peripheral blood(one year post infusion of IMA203)
- Objective response rate (ORR)(one year post infusion of IMA203)