A Phase 1 Dose Escalation and Expanded Cohort Study of P-PSMA-101 in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC) and Advanced Salivary Gland Cancers (SGC)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 40
- 试验地点
- 10
- 主要终点
- Assess the Safety of P-PSMA-101
研究概览
简要总结
An open-label, multi-center, single and cyclic ascending dose study of P-PSMA-101 autologous CAR-T cells in patients with mCRPC and SGC.
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-PSMA-101 to determine a Recommended Phase 2 Dose (RP2D). Additional participants will be treated with P-PSMA-101 at the determined RP2D.
Following consent, enrolled participants will undergo a leukapheresis procedure to obtain peripheral blood mononuclear cells (PBMCs) which will be sent to a manufacturing site to produce P-PSMA-101 CAR-T cells. The cells will then be returned to the investigational site and administered after a lymphodepleting chemotherapy regimen. 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
- •Subjects ≥18 years of age
- •Must have a confirmed diagnosis of mCRPC or SGC
- •Must have measurable disease by RECIST 1.1 or bone only metastases with measurable PSA (≥1 ng/mL) (mCRPC subjects only)
- •Must have progressed by PCWG3 and/or RECIST 1.1 (mCRPC subjects only)
- •Must be willing to practice birth control from screening and for 2 years after the last administration of P-PSMA-101
- •Must have adequate vital organ function within pre-determined parameters
- •Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
排除标准
- •Has inadequate venous access and/or contraindications to leukapheresis
- •Has an active second malignancy in addition to mCRPC or SGC, excluding low-risk neoplasms such as non-metastatic basal cell or squamous cell skin carcinoma
- •Has a history of or active autoimmune disease
- •Has a history of significant central nervous system (CNS) disease, such as stroke or epilepsy
- •Has an active systemic (viral, bacterial or fungal) infection
- •Has received anti-cancer medications (excluding GnRH targeted therapies) within 2 weeks of the time of initiating conditioning chemotherapy
- •Has received immunosuppressive medications (including anti-cancer medications) within 2 weeks of initiating leukapheresis and/or expected to require them while enrolled in the study
- •Has received systemic corticosteroid therapy within 2 weeks of either the required leukapheresis or is expected to require it during the course of the study
- •Has CNS metastases or symptomatic CNS involvement
- •Has a history of significant ocular disease
- •Has a history of significant liver disease or active liver disease
- •Has liver metastases (<5 lesions and maximum diameter </= 2.5 cm permitted)
- •Has a history of or known predisposition to HLH or MAS
研究组 & 干预措施
P-PSMA-101 CAR-T cells (Single Dose - Part 1a)
Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following conditioning chemotherapy regimen A. Rimiducid may be administered as indicated.
干预措施: P-PSMA-101 CAR-T cells (Biological)
P-PSMA-101 CAR-T cells (Single Dose - Part 1a)
Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following conditioning chemotherapy regimen A. Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-PSMA-101 CAR-T cells (Multiple Dose - Part 1b)
Cyclic administration of ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following conditioning chemotherapy regimen A. Rimiducid may be administered as indicated.
干预措施: P-PSMA-101 CAR-T cells (Biological)
P-PSMA-101 CAR-T cells (Multiple Dose - Part 1b)
Cyclic administration of ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following conditioning chemotherapy regimen A. Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-PSMA-101 CAR-T cells (Single Dose - Part 1c)
Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following conditioning chemotherapy regimen B. Rimiducid may be administered as indicated.
干预措施: P-PSMA-101 CAR-T cells (Biological)
P-PSMA-101 CAR-T cells (Single Dose - Part 1c)
Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells, following conditioning chemotherapy regimen B. Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-PSMA-101 CAR-T cells (Multiple Dose - Part 1d)
Cyclic administration of ascending dose cohorts, given via intravenous infusions of CAR-T cells, following conditioning chemotherapy regimen B. Rimiducid may be administered as indicated.
干预措施: P-PSMA-101 CAR-T cells (Biological)
P-PSMA-101 CAR-T cells (Multiple Dose - Part 1d)
Cyclic administration of ascending dose cohorts, given via intravenous infusions of CAR-T cells, following conditioning chemotherapy regimen B. Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
结局指标
主要结局
Assess the Safety of P-PSMA-101
时间窗: Baseline through 15 years
Incidence and severity of treatment-emergent adverse events
Determine the maximum tolerated dose of P-PSMA-101
时间窗: Baseline through Day 28
Rate of dose limiting toxicities (DLT)
Assess the efficacy of P-PSMA-101 (ORR)
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), and Prostate Cancer Response assessed by Prostate Cancer Working Group 3 (PCWG3) criteria: Overall Response Rate (ORR)-Percentage of patients with complete response (CR) or partial response (PR).
次要结局
未报告次要终点