肿瘤细胞治疗研究
英文原题：TmPSMA-02 in mCRPC
这是一项 I 期注册临床试验，评估 CAR-T 细胞治疗前列腺癌的安全性、可行性及初步疗效。当前状态：进行中（不再招募）。计划入组 30 例。试验地点：美国 · 费城（共 1 个中心）。登记号：NCT06046040。
仅男性 · ≥ 18 Years
入选标准 1. 已签署书面知情同意书。 2. 成年受试者，年龄≥18岁。 3. 转移性去势抵抗性前列腺癌（mCRPC）。 4. 睾酮达到去势水平（<50 ng/dL），可使用或不使用雄激素剥夺治疗。 5. 在mCRPC阶段至少接受过一种全身标准治疗，包括至少一种第二代雄激素受体信号通路抑制剂（如enzalutamide、apalutamide、darolutamide或abiraterone）或紫杉烷类方案（如docetaxel、cabazitaxel等）。 6. 医师研究者确认符合入选资格前4周内器官功能充分：血清肌酐≤1.5 mg/dL，或按Cockcroft-Gault公式计算的肌酐清除率≥50 cc/min，且未接受透析；ALT/AST≤ULN的3倍；血清总胆红素≤1.5 mg/dL，Gilbert综合征者≤3.0 mg/dL；超声心动图确认左心室射血分数（LVEF）≥45%；肺储备充分，呼吸困难≤1级且室内空气下脉搏血氧>92%。 7. 医师研究者确认入选资格前4周内血液学储备充分，且不依赖输血维持指标：血红蛋白≥8 g/dL；中性粒细胞绝对计数≥1000/μL；血小板≥75,000/μL。 8. ECOG体能状态为0或1。 9. 未接受双侧睾丸切除术者，须能够在研究期间继续接受促性腺激素释放激素（GnRH）治疗。 10. 有生育能力的受试者须同意采用方案所述的可接受避孕方法。 排除标准 1. 活动性乙型或丙型肝炎感染。 2. 任何其他活动性、未控制的感染。 3. 按纽约心脏协会（NYHA）分级为III或IV级的心血管功能障碍。 4. 医师研究者认为会妨碍参加研究的严重活动性合并症。 5. 医师研究者确认入选资格前2年内患有除本研究目标癌症以外的活动性浸润性肿瘤。注：以根治为目的治疗的非浸润性肿瘤（如非黑色素瘤皮肤癌）仍可能符合入选条件。 6. 需长期全身使用类固醇或免疫抑制药物者。允许低剂量生理替代治疗（相当于泼尼松≤10 mg/日）、局部类固醇及吸入类固醇。类固醇和免疫抑制药物使用详情见方案第5.6节。 7. 既往接受自体T细胞治疗者，Sipuleucel-T除外。 8. 既往接受异基因造血干细胞移植。 9. 活动性自身免疫病需全身免疫抑制治疗（相当于泼尼松≥10 mg）；自身免疫性神经系统疾病（如多发性硬化症）患者排除。 10. 对研究产品辅料（人血清白蛋白、DMSO或右旋糖酐40）有过敏或超敏反应史。
Inclusion Criteria: 1. Signed, written informed consent 2. Adult participants ≥ 18 years of age 3. Metastatic castrate-resistant prostate cancer (mCRPC) 4. Castrate levels of testosterone (\<50 ng/dL) with/without the use of androgen-deprivation therapy 5. Received at least one prior standard therapy for systemic treatment in the mCRPC setting, including at least one second generation androgen receptor signaling inhibitor (e.g., enzalutamine, apalutamide, darolutamide, or abiraterone) or a taxane-based regimen (e.g., docetaxel, cabazitaxel, etc). 6. Adequate organ function within 4 weeks of eligibility confirmation by a physician-investigator defined as: 1. Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 50 cc/min per the Cockcroft-Gault Equation; Patient must not be on dialysis 2. ALT/AST ≤ 3 x ULN 3. Serum total bilirubin ≤ 1.5 mg/dL, unless the subject has Gilbert's syndrome (if so, serum total bilirubin must be ≤3.0 mg/dL) 4. Left Ventricle Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO 5. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen \> 92% on room air 7. Patients must have adequate hematologic reserve within 4 weeks of eligibility confirmation by a physician-investigator and must not be dependent on transfusions to maintain these hematologic parameters. Adequate hematologic reserve is defined as: 1. Hemoglobin ≥ 8 g/dL 2. Absolute neutrophil count ≥ 1000/μL 3. Platelet count ≥ 75,000/μL 8. ECOG Performance Status that is either 0 or 1. 9. Patients who have not undergone bilateral orchiectomy must be able to continue GnRH therapy during the study. 10. Participants of reproductive potential must agree to use acceptable birth control methods, as described in the protocol. Exclusion Criteria: 1. Active hepatitis B or hepatitis C infection 2. Any other active, uncontrolled infection 3. Class III/IV cardiovascular disability according to the New York Heart Association Classification. 4. Severe, active co-morbidity that in the opinion of the physician-investigator would preclude participation in the study. 5. Active invasive cancer, other than the proposed cancer included in the study, within 2 years prior to eligibility confirmation by a physician-investigator. \[Note: non-invasive cancers treated with curative intent (e.g., non-melanoma skin cancer) may still be eligible\]. 6. Patients requiring chronic treatment systemic steroids or immunosuppressant medications. Low-dose physiologic replacement therapy with corticosteroids equivalent to prednisone 10 mg/day or lower, topical steroids and inhaled steroids are acceptable. For additional details regarding use of steroid and immunosuppressant medications, please see Section 5.6. 7. Prior treatment with autologous T-cell therapy, with the exception of Sipuleucel-T. 8. Prior allogeneic stem cell transplant. 9. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded. 10. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
以上为辅助阅读译文。是否适合入组须由主治医生判断，最终以登记平台与研究者确认为准。
主要终点：Number of subjects with dose limiting toxicities (DLTs) · 28 days after TmPSMA-02 CAR T cell infusion；Determination of maximum tolerated dose (MTD) · 28 days after TmPSMA-02 CAR T cell infusion；Incidence of Adverse Events as assessed by CTCAE v5.0 · Up to 15 years
次要终点：Percentage of manufacturing products that meet release criteria；Overall Response Rate (ORR)；Duration of Response (DOR)；Progression Free Survival (PFS)；Overall Survival (OS)；Percent Change in PSA from Baseline
淋巴清除化疗后给予1×10^7个TmPSMA-02 CAR-T细胞。
淋巴清除化疗后给予5×10^7个TmPSMA-02 CAR-T细胞。
淋巴清除化疗后给予1×10^8个TmPSMA-02 CAR-T细胞。
淋巴清除化疗后给予3×10^8个TmPSMA-02 CAR-T细胞。
这是一项I期开放标签剂量探索研究，旨在评估TmPSMA-02 CAR-T细胞治疗转移性去势抵抗性前列腺癌（mCRPC）的安全性、耐受性、制备可行性及初步疗效。研究采用3+3剂量递增设计，最多评估4个剂量水平。
This is a Phase I, open-label dose finding study to assess the safety, tolerability, manufacturing feasibility, and preliminary efficacy of TmPSMA-02 CAR T cells in patients with metastatic castrate-resistant prostate cancer (mCRPC). Up to 4 total dose levels will be evaluated using a 3+3 dose escalation design.
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