A Single-Center, Open-Label, Single-Arm, Exploratory Clinical Study to Evaluate the Safety and Efficacy of Allogeneic CAR-NK Cell Therapy in Metastatic Castration-Resistant Prostate Cancer (mCRPC)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Occurrence of treatment related adverse events as assessed by CTCAE v5.0
研究概览
简要总结
This study introduces a new treatment approach for metastatic castration-resistant prostate cancer, a stage of disease that remains difficult to manage with current therapies. Prostate cancer is the second most common cancer in men worldwide, and many patients eventually progress to an advanced, treatment-resistant stage despite hormone therapy, newer hormonal agents, or chemotherapy. Patients with metastatic castration-resistant disease often face a poor prognosis, complications such as bone metastases, and significant impacts on quality of life, highlighting the urgent need for new treatment options. This research focuses on an innovative immunotherapy using allogeneic anti-PSMA CAR-NK cells, which are engineered natural killer cells designed to precisely recognize and kill prostate cancer cells expressing the prostate-specific membrane antigen. CAR-NK cells combine the natural tumor-killing ability of NK cells with enhanced targeting and reduced immune escape, offering a potentially safer and more effective strategy. Through this clinical study, the safety, tolerability, and preliminary effectiveness of anti-PSMA CAR-NK cell therapy will be evaluated, aiming to provide new evidence and expand future treatment possibilities for patients with advanced prostate cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Age ≥ 18 years, male;
- •Diagnosis of metastatic castration-resistant prostate cancer (mCRPC) meeting the following criteria: ① Serum testosterone at castration level: < 50 ng/dL or < 1.7 nmol/L; ② Meeting any one of the following conditions: a. PSA progression: Three consecutive rises in PSA measured at intervals of at least 1 week, with two increases being ≥ 50% above the PSA nadir, and a PSA value > 2 ng/mL; b. Radiographic progression: Two or more new lesions detected on bone scan, or an increase in soft tissue lesions assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST).
- •Expected survival ≥ 6 months;
- •ECOG performance status of 0-2;
- •Positive prostate-specific membrane antigen (PSMA) expression;
- •Voluntarily participate, provide written informed consent, and be able to comply with follow-up.
排除标准
- •Prior treatment with other cell therapy products besides the investigational product, such as dendritic cells (DC), cytokine-induced killer cells (CIK), T cells, natural killer cells (NK), chimeric antigen receptor T-cell immunotherapy (CAR-T), etc.;
- •History of other malignancies within 5 years prior to screening (except for completely resolved carcinoma in situ or malignancies deemed by the investigator to be slow-progressing);
- •Abnormal function of major organs: a. Absolute neutrophil count (ANC) < 1.5 × 10⁹/L; Platelet count (Plt) < 100 × 10⁹/L; Hemoglobin (Hb) < 9 g/dL; b. Liver function: Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≥ 2.5 × the upper limit of normal (ULN) (or ≥ 5 × ULN for subjects with liver metastases); c. Renal function: Serum creatinine (Cr) ≥ 1.5 × ULN; d. Coagulation function: Prothrombin time (PT), Activated partial thromboplastin time (APTT), International Normalized Ratio (INR) ≥ 1.5 × ULN;
- •Any currently treated active (viral, bacterial, fungal) infection, or any infection within the past 6 weeks requiring intravenous antibiotics for 7 days or longer, or any active infection requiring oral antibiotics within the past week;
- •Active autoimmune disease, or history of severe autoimmune disease requiring long-term immunosuppressive therapy;
- •Participation in another clinical trial study within 3 months;
- •Inability to employ effective contraceptive measures;
- •History of hypersensitivity to biologic macromolecular drugs;
- •Untreated chronic active hepatitis B, or chronic hepatitis B virus carriers with HBV DNA ≥ 1000 copies/mL, or patients with active hepatitis C;
- •Subjects deemed by the investigator to be unsuitable for participation in this study for other reasons.
研究组 & 干预措施
Experimental group
干预措施: anti-PSMA CAR-NK (Biological)
结局指标
主要结局
Occurrence of treatment related adverse events as assessed by CTCAE v5.0
时间窗: Baseline to 1 year post infusion
Defined as \>= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment
次要结局
- The pharmacodynamics analysis of Anti-PSMA CAR NK Cell(Baseline to infusion date、Day0、Day1、Day2、Day7、Day8、Day9、Day14、Day15、Day16、Day21、Day28、Day60、Day90、Day120、Day180、Day270 and Day360)
- Time to clinical progression(Baseline to Day28、Day90、Day180、Day270 and Day360 post infusion)
- The pharmacokinetic analysis of Anti-PSMA CAR-NK Cell(Day-2-Day-1、Day0、Day2、Day7、Day9、Day14、Day16、Day21、Day28、Day60 and Day90 post infusion)
- The proportion of patients with a decrease in PSA levels from baseline(Baseline toDay0、Day1、Day2、Day7、Day8、Day9、Day14、Day15、Day16、Day21、Day28、Day60、Day90、Day120、Day180、Day270 and Day360 post infusion)
- Progression-free survival (PFS) after Anti-PSMA CAR NK Cell infusion(Baseline to 1 year post infusion)
研究者
XINGNIANZENG
Vice President of the Hospital
Cancer Institute and Hospital, Chinese Academy of Medical Sciences