A Phase 1 Dose Escalation and Expanded Cohort Study of P-MUC1C-ALLO1 in Adult Subjects With Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 180
- 试验地点
- 27
- 主要终点
- Determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of P-MUC1C-ALLO1
研究概览
简要总结
A Phase 1, open label, dose escalation and expanded cohort study of P-MUC1C-ALLO1 in adult subjects with advanced or metastatic epithelial derived solid tumors, including but not limited to the tumor types listed below.
详细描述
This is an open label, multi-center Phase 1 study that will follow a 3 + 3 design of dose-escalating cohorts of single and multiple doses of P-MUC1C-ALLO1 to determine a Recommended Phase 2 Dose (RP2D). P-MUC1C-ALLO1 is an allogeneic chimeric antigen receptor (CAR) T cell therapy designed to target cancer cells expressing Mucin1 cell surface associated C-Terminal (MUC1-C) antigen. Additional participants will be treated with P-MUC1C-ALLO1 at the determined RP2D.
Following enrollment, subjects will be treated with P-MUC1C-ALLO1 and will undergo serial measurements of safety, tolerability and response. Rimiducid may be administered as indicated.
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
- •Males or females, Subjects ≥18 years with life expectancy >3 months
- •Must have a confirmed diagnosis of unresectable, locally advanced or metastatic epithelial-derived cancer
- •Must have progressed during or after last therapy, developed intolerance/toxicity to current treatment, or ineligible or refused other existing treatment options, and have measurable disease
- •Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 or Karnofsky performance status ≥70%
- •Must have adequate vital organ function within pre-determined parameters
- •Must have archived tumor tissue available or consent to a biopsy collection
- •Must be willing to practice birth control
- •Must have a negative pregnancy test at screening and prior to initiating lymphodepletion chemotherapy or study drug administration
- •Must have recovered from toxicities due to prior therapies
排除标准
- •Has inadequate venous access
- •Has an active second malignancy (not disease free for at least 5 years) in addition to the studied malignancy, excluding low-risk neoplasms such as non-metastatic basal cell or squamous cell skin carcinoma
- •Is pregnant or lactating
- •Has a history of or active autoimmune disease
- •Has a history of significant central nervous system (CNS) disease, such as stroke, epilepsy
- •Has an active systemic (viral, bacterial, or fungal) infection
- •Has New York Heart Association (NYHA) Class III or IV heart failure, unstable angina, or a history of myocardial infarction or significant arrhythmia
- •Has any psychiatric or medical disorder that would preclude safe participation in and/or adherence to the protocol
- •Has received anticancer medications within 2 weeks of the time of initiating lymphodepletion
- •Has received immunosuppressive medications within 2 weeks of administration of P-MUC1C-ALLO1, and/or expected to require them while enrolled in the study
- •Has received systemic corticosteroid therapy within 1 week of the administration of P-MUC1C-ALLO1 or is expected to require it during the course of the study
- •Has known CNS metastases or symptomatic CNS involvement
- •Has a history of significant liver disease or active liver disease
- •Has a history of known genetic predisposition to HLH/MAS
- •Has received anti-cancer monoclonal antibody therapy within 4 weeks of initiating LD therapy
研究组 & 干预措施
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm C)
- Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 2.
- Rimiducid may be administered as indicated.
干预措施: P-MUC1C-ALLO1 CAR-T cells (Biological)
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm A)
- Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 1.
- Rimiducid may be administered as indicated.
干预措施: P-MUC1C-ALLO1 CAR-T cells (Biological)
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm A)
- Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 1.
- Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm B)
- Cyclic administration of ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 1.
- Rimiducid may be administered as indicated.
干预措施: P-MUC1C-ALLO1 CAR-T cells (Biological)
P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm B)
- Cyclic administration of ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 1.
- Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm C)
- Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 2.
- Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm D)
- Cyclic administration of ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 2.
- Rimiducid may be administered as indicated.
干预措施: P-MUC1C-ALLO1 CAR-T cells (Biological)
P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm D)
- Cyclic administration of ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 2.
- Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm A1)
- Single ascending A1 dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 1.
- Rimiducid may be administered as indicated.
干预措施: P-MUC1C-ALLO1 CAR-T cells (Biological)
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm A1)
- Single ascending A1 dose cohorts, given in a single intravenous infusion of CAR-T cells, following lymphodepletion regimen 1.
- Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm E)
- Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following assigned lymphodepletion regimen.
- Rimiducid may be administered as indicated.
干预措施: P-MUC1C-ALLO1 CAR-T cells (Biological)
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm E)
- Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following assigned lymphodepletion regimen.
- Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm F)
- Cyclic administration of ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following assigned lymphodepletion regimen.
- Rimiducid may be administered as indicated.
干预措施: P-MUC1C-ALLO1 CAR-T cells (Biological)
P-MUC1C-ALLO1 CAR-T cells (Multiple Dose - Arm F)
- Cyclic administration of ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following assigned lymphodepletion regimen.
- Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm M)
- Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following assigned lymphodepletion regimen.
- Rimiducid may be administered as indicated.
干预措施: P-MUC1C-ALLO1 CAR-T cells (Biological)
P-MUC1C-ALLO1 CAR-T cells (Single Dose - Arm M)
- Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following assigned lymphodepletion regimen.
- Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
结局指标
主要结局
Determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of P-MUC1C-ALLO1
时间窗: Baseline through Day 28
Number of subjects with a dose limiting toxicity (DLT)
Evaluate the overall safety and tolerability profile of P-MUC1C-ALLO1
时间窗: Baseline through 15 years
Frequency and severity of adverse events
Evaluate the preliminary efficacy of P-MUC1C-ALLO1
时间窗: Baseline through 15 years
According to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, secondarily Immune Response Evaluation Criteria in Solid Tumors (iRECIST): Overall Response Rate (ORR)
次要结局
未报告次要终点