First Time-in-Human (FTiH), Phase I Trial to Evaluate the Safety, Cellular Kinetics, and Efficacy of A-CAR032, in Adult Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
概览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Shanghai AbelZeta Ltd.
- 入组人数
- 27
- 试验地点
- 5
- 主要终点
- Dose Escalation (Part 1)：Safety
概览
简要总结
This FTiH, single-arm, open-label, investigator-initiated Phase I trial will evaluate the safety, antitumour activity, CK/pharmacodynamics (PD), biomarkers, immunogenicity, and feasibility of A-CAR032 in adult participants with mCRPC, who have previously progressed after ARPI treatment of prostate cancer (whether before or in the metastatic castration-resistant setting) and, in the judgment of the investigator, are ineligible for standard treatment.
详细描述
The study consists of two parts: Part 1-Dose Escalation and Part 2-Dose Expansion. Participants in the study will proceed through screening, apheresis, bridging therapy (if appropriate), lymphodepletion, CAR-T cell infusion, and subsequent follow-up (including Stage 1, 2 and 3).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- Male
- 接受健康志愿者
- 否
入选标准
- •Participant must be 18 years or older at the time of signing the ICF. Type of Participant and Disease Characteristics
- •Participants with:
- •A histologically confirmed diagnosis of metastatic adenocarcinoma of the prostate without known neuroendocrine differentiation or small cell features.
- •Castration-resistant prostate cancer as defined by disease progression despite castration by orchiectomy or ongoing luteinising hormone-releasing hormone analogue. Participants receiving medical castration therapy with gonadotropin-releasing hormone analogues should continue this treatment during the study.
- •Measurable PSA≥1 ng/mL AND
- •Evidence of progression within 6 months prior to screening
- •Participant has previously received an ARPI (ie, abiraterone, enzalutamide, apalutamide, darolutamide, rezvilutamide) whether before or in the metastatic castration-resistant setting, and in the judgment of the investigator, be ineligible for standard treatment.
- •Minimum life expectancy of \> 12 weeks prior to apheresis in the opinion of the investigator.
- •Adequate organ and marrow function
- •Consent and provision of tumour material to assess STEAP2 expression and other correlative biomarkers retrospectively with pre- and post-treatment biopsies.
排除标准
- •Known life-threatening allergies, hypersensitivity, or intolerance to the CAR-T product or its excipients, including dimethyl sulfoxide (DMSO).
- •Contraindication to lymphodepleting agents, including fludarabine and/or cyclophosphamide.
- •History of another primary malignancy except for:
- •Malignancy treated with curative intent and with no known active disease within 3 years before the apheresis and of low potential risk for recurrence.
- •Adequately treated non-melanoma skin cancer or lentigo malignancy without evidence of disease.
- •Adequately treated carcinoma in situ without evidence of disease.
- •Participants with known brain metastases.
- •History of splenectomy or organ transplantation.
- •Prior treatment with:
- •Any CAR-T therapy. OR
结局指标
主要结局
Dose Escalation (Part 1)：Safety
时间窗: From ICF signature until 15 years post A-CAR032 infusion
Incidence of AEs/SAEs
Dose Escalation (Part 1)：Safety
时间窗: Throughout the 28 days post A-CAR032 infusion
Occurrence of DLTs/DLT-like events
Dose Escalation (Part 1)：Safety
时间窗: From ICF signature until 12 months post A-CAR032 infusion
Changes from baseline in laboratory parameters, vital signs, and ECGs
Dose Expansion (Part 2)：Safety
时间窗: From ICF signature until 15 years post A-CAR032 infusion
Incidence of AEs/SAEs
Dose Expansion (Part 2)：Safety
时间窗: Throughout the 28 days post A-CAR032 infusion
Incidence of DLT-like events
Dose Expansion (Part 2)：Safety
时间窗: From ICF signature until 12 months post A-CAR032 infusion
Changes from baseline in laboratory parameters, vital signs, and ECGs
次要结局
- Dose Escalation (Part 1) and Dose Expansion (Part 2)：Efficacy(From ICF signature until 12 months post A-CAR032 infusion)
- Dose Escalation (Part 1) and Dose Expansion (Part 2)：Efficacy(From ICF signature until 15 years post A-CAR032 infusion)
- Dose Escalation (Part 1) and Dose Expansion (Part 2)：Efficacy(From A-CAR032 infusion until 12 months post A-CAR032 infusion)
- Dose Escalation (Part 1) and Dose Expansion (Part 2)：Pharmacokinetics(From ICF signature until 15 years post A-CAR032 infusion)