A Phase 1a/1b, Open-label First-in-human Study of the Safety, Tolerability and Feasibility of Gene-edited Autologous NeoTCR-T Cells (NeoTCR-P1) Administered as a Single Agent or in Combination With Anti-PD-1 to Patients With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 暂停
- 入组人数
- 21
- 试验地点
- 17
- 主要终点
- Incidence of adverse events as defined as DLTs
研究概览
简要总结
This is a first in human, single arm, open label, Phase 1a/1b study to determine the safety, feasibility, and efficacy of a single dose of NeoTCR-P1 T cells in participants with solid tumors.
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
- •Histologically or cytologically documented incurable or metastatic solid tumors of the following types: melanoma, UC, ovarian cancer, colorectal cancer, breast cancer (HR+), or prostate cancer.
- •Disease has progressed after at least one available standard therapy or no additional curative therapies are available.
- •Measurable disease per RECIST v1.1
- •Eastern cooperative oncology group (ECOG) performance status of 0 or 1
- •Adequate hematologic and end organ function determined within 30 days prior to enrollment.
- •Disease-specific criteria related to the specific tumor type are required.
- •Note: There are additional inclusion criteria. The study center will determine if you meet all of the criteria.
排除标准
- •Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, and/or inherited liver disease
- •Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases
- •Uncontrolled or symptomatic hypercalcemia
- •Pregnancy, lactation, or breastfeeding
- •Prior allogeneic stem cell transplant or solid organ transplant
- •Prior chimeric antigen receptor therapy or other genetically modified T cell therapy
- •Active HIV, Hepatitis B, or Hepatitis C infection
- •Active tuberculosis
- •Severe infection within 2 weeks prior to enrollment
- •Major surgical procedure within 4 weeks prior to enrollment or anticipation of need for a major surgical procedure during the study.
- •Note: There are additional exclusion criteria. The study center will determine if you meet all of the criteria.
结局指标
主要结局
Incidence of adverse events as defined as DLTs
时间窗: 28 days
Dose limiting toxicity (DLT) is defined as protocol-defined adverse events that occur within 28 days following infusion of Neo-TCR-P1 administered as a single agent without or with IL-2, or in combination with nivolumab.
Number of participants with adverse events as a measure of safety and tolerability of NeoTCR-P1 or NeoTCR-P1 in combination with nivolumab
时间窗: 2 years
Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). Cytokine release syndrome (CRS) and neurotoxicity associated with NeoTCR-P1 will be graded according to ASBMT consensus grading.
Maximum Tolerated Dose (MTD) of NeoTCR-P1
时间窗: 2 years
The MTD is defined as the highest dose with an observed incidence of DLT in no more than one out of six patients treated at a particular dose level.
Feasibility of manufacturing NeoTCR-P1
时间窗: 2 years
Percent of screened patients that enroll on study and receive NeoTCR-P1
次要结局
- Maximum concentration of NeoTCR-P1 (Cmax) in the peripheral blood(2 years)
- Area-under-the-concentration-vs-time-curve (AUC) in the peripheral blood(28 days)
- Persistence of NeoTCR-P1 in samples of peripheral blood(2 years)
- Objective Response Rate (ORR) in participants with solid tumors following infusion of NeoTCR-P1 as a single agent or in combination with nivolumab(2 years)
- Duration of Response mediated by neoTCR-P1 administered as a single agent or in combination with nivolumab to participants with solid tumors(2 years)
- Progression free survival (PFS) in participants with solid tumors following infusion of NeoTCR-P1 as a single agent or in combination with nivolumab(2 years)
- Overall survival (OS) in participants with solid tumors following infusion of NeoTCR-P1 as a single agent or in combination with nivolumab(2 years)