Phase 1/2 Study Evaluating Genetically Modified Autologous T Cells Expressing a TCR Recognizing a Cancer/Germline Antigen as Monotherapy or in Combination With Nivolumab 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
- 375
- 试验地点
- 31
- 主要终点
- Phase 1 and Phase 2: Number and grade of treatment emergent adverse events and adverse events of special interest in subjects treated.
研究概览
简要总结
The study's purpose is to establish the safety and tolerability of IMA203/IMA203CD8 products with or without combination with nivolumab in patients with solid tumors that express preferentially expressed antigen in melanoma (PRAME).
详细描述
SCREENING: Patient eligibility will be determined by protocol inclusion/exclusion criteria including HLA (human leukocyte antigen) screening and a biopsy (or collection of archival tumor tissue) for biomarker screening. If the patient is eligible, white blood cells will be taken during leukapheresis for the manufacture of IMA203 or IMA203CD8 product.
MANUFACTURING: IMA203 or IMA203CD8 products will be made from the patients' white blood cells.
TREATMENT: Lymphodepletion with cyclophosphamide and fludarabine will occur in the days before the IMA203/IMA203CD8 product infusion to improve the duration of time that IMA203/IMA203CD8 product stays in the body. The patient will be admitted to the hospital during the T-cell infusion.
After the IMA203/IMA203CD8 product infusion, if applicable, a low dose of IL-2 will be given subcutaneously until day 10.
In Extension Cohort B (IMA203) nivolumab will be administered intravenously.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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 must have recurrent/progressing and/or refractory solid tumors and must have received or not be eligible for all available indicated standard of care treatment.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •HLA-A*02:01 positive
- •For patients with ovarian/fallopian tube cancer only: Patients must have confirmed diagnosis of high-grade serous or endometrioid epithelial ovarian cancer (EOC), primary peritoneal cancer, or fallopian tube cancer.
- •For patients with endometrial carcinoma only: Patients must have a histologically confirmed diagnosis of recurrent or persistent endometrial carcinoma.
- •Measurable disease according to RECIST 1.1
- •Adequate selected organ function per protocol
- •Patient's tumor must express tumor antigen by "IMADetect® RT-qPCR. Retrospective testing will be required for patients that qualify.
- •Life expectancy more than 5 months
- •Female patient of childbearing potential must use adequate contraception prior to study entry until 12 months after the infusion of IMA203/IMA203CD8
- •Male patient must agree to use effective contraception or be abstinent while on study and for 6 months after the infusion of IMA203/IMA203CD8
- •The patient must have recovered from any side effects of prior therapy to Grade 1 or lower prior to lymphodepletion.
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 Note: At the discretion of the investigator, these patients may be included if their disease is well controlled without the use of immunosuppressive agents.
- •History of cardiac conditions as per protocol
- •Prior stem cell transplantation or solid organ transplantation
- •Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study
- •History of or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician
- •Positive for HIV infection or with active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
- •Patients with LDH greater than 2.0-fold ULN.
- •Any condition contraindicating leukapheresis, lymphodepletion, low-dose IL-2, and/or IMA203/IMA203CD8 treatment
- •Patients with active brain metastases
- •Concurrent treatment in another clinical trial.
- •For nivolumab treatment, patients must not have a history of severe immune-related toxicities, defined as any Grade 3 or 4 toxicities related to prior PD1/PD-L1 inhibitor therapy (e.g., atezolizumab, pembrolizumab or nivolumab etc.).
- •Other protocol defined inclusion/exclusion criteria could apply
研究组 & 干预措施
Extension Cohort D
IMA203CD8 at dose levels confirmed to be safe; without IL-2
干预措施: IMA203CD8 Product (Biological)
Dose Escalation A (closed to enrollment)
Dose escalation of IMA203
干预措施: IMA203 Product (Biological)
Dose Escalation A (closed to enrollment)
Dose escalation of IMA203
干预措施: IMADetect® (Device)
Extension Cohort A
IMA203 at RP2D
干预措施: IMA203 Product (Biological)
Extension Cohort B (closed to enrollment)
IMA203 at RP2D + nivolumab
干预措施: Nivolumab (Drug)
Ovarian
IMA203CD8 monotherapy at dose levels confirmed to be safe
干预措施: IMA203CD8 Product (Biological)
Extension Cohort D
IMA203CD8 at dose levels confirmed to be safe; without IL-2
干预措施: IMADetect® (Device)
Ovarian
IMA203CD8 monotherapy at dose levels confirmed to be safe
干预措施: IMADetect® (Device)
Endometrial
IMA203CD8 monotherapy at dose levels confirmed to be safe
干预措施: IMA203CD8 Product (Biological)
Endometrial
IMA203CD8 monotherapy at dose levels confirmed to be safe
干预措施: IMADetect® (Device)
Head and Neck, Lung, and Triple Negative Breast Cancer
IMA203CD8 monotherapy at dose levels confirmed to be safe
干预措施: IMA203CD8 Product (Biological)
Head and Neck, Lung, and Triple Negative Breast Cancer
IMA203CD8 monotherapy at dose levels confirmed to be safe
干预措施: IMADetect® (Device)
Extension Cohort AA
IMA203 at final RP2D (flat dose)
干预措施: IMA203 product- flat dose (Biological)
Extension Cohort A
IMA203 at RP2D
干预措施: IMADetect® (Device)
Extension Cohort B (closed to enrollment)
IMA203 at RP2D + nivolumab
干预措施: IMA203 Product (Biological)
Extension Cohort AA
IMA203 at final RP2D (flat dose)
干预措施: IMADetect® (Device)
Uveal Melanoma
IMA203 at RP2D
干预措施: IMA203 Product (Biological)
Rare Cancers
IMA203CD8 monotherapy at dose levels confirmed to be safe
干预措施: IMADetect® (Device)
Uveal Melanoma
IMA203 at RP2D
干预措施: IMADetect® (Device)
Dose Escalation B
Dose escalation of IMA203CD8
干预措施: IMA203CD8 Product (Biological)
Dose Escalation B
Dose escalation of IMA203CD8
干预措施: IMADetect® (Device)
Extension Cohort C
IMA203CD8 at dose levels confirmed to be safe
干预措施: IMA203CD8 Product (Biological)
Extension Cohort C
IMA203CD8 at dose levels confirmed to be safe
干预措施: IMADetect® (Device)
Rare Cancers
IMA203CD8 monotherapy at dose levels confirmed to be safe
干预措施: IMA203CD8 Product (Biological)
结局指标
主要结局
Phase 1 and Phase 2: Number and grade of treatment emergent adverse events and adverse events of special interest in subjects treated.
时间窗: 35 days
Treatment emergent adverse events (TEAEs), Adverse events of special interest (AESIs) and Treatment-emergent serious adverse events (TESAEs).
Phase 1 and Phase 2: Tumor Response
时间窗: 5 years
Objective response rate (ORR) based on best overall response (BOR) of complete response (CR) and partial response (PR) centrally assessed (by a BICR1) using RECIST1.1
Phase 1: Determine the MTD and/or recommended dose for extension for IMA203/IMA203CD8
时间窗: 28 days
Number of patients with dose-limiting toxicities (DLTs)
Phase 1: Determine the MTD and/or recommended dose for extension for IMA203/IMA203CD8
时间窗: 28 days
Number of patients with dose-limiting toxicities (DLTs)
Phase 1 and Phase 2: Number and grade of treatment emergent adverse events and adverse events of special interest in subjects treated.
时间窗: 35 days
Treatment emergent adverse events (TEAEs), Adverse events of special interest (AESIs) and Treatment-emergent serious adverse events (TESAEs).
Phase 1 and Phase 2: Tumor Response
时间窗: 5 years
Objective response rate (ORR) based on best overall response (BOR) of complete response (CR) and partial response (PR) centrally assessed (by a BICR1) using RECIST1.1
次要结局
- Phase 1 and 2: Tumor response(up to 5 years)
- Phase 1 and 2: Persistence of TCR engineered T-cells(up to 5 years post treatment)
- Phase 2: Patient reported quality of life(up to 5 years)
- Phase 1 and 2: Persistence of TCR engineered T-cells(up to 5 years post treatment)
- Phase 1 and 2: Tumor response(up to 5 years)
- Phase 2: Patient reported quality of life(up to 5 years)