CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria

1. understanding of this study and voluntarily signs the informed consent form;
2. Aged ≥ 18 years;
3. Expected survival time of at least 3 months;
4. non-metastatic CRPC (nmCRPC) (local recurrence) or metastatic CRPC (mCRPC)；
5. continue GnRH analog therapy；
6. at least one evaluable lesion per RECIST 1.1;
7. Has received at least one type of novel endocrine therapy；
8. PSMA positive expression rate \> 10%;
9. Eastern Cooperative Oncology Group (ECOG) 0-1;
10. Well organ function
11. Left Ventricular Ejection Fraction (LVEF) \> 50%;
12. Oxygen saturation \> 92% without oxygen supplementation;
13. agree to use effective contraceptive measures

Exclusion Criteria

1. Presence of brain metastasis;
2. Organ transplantation or pending organ transplantation;
3. Uncontrolled large-volume serous cavity effusions；
4. A history of autoimmune diseases；
5. A history of receiving other cell therapies or genetically modified cell therapies (e.g., TCR-T therapy, CAR-T therapy);
6. A history of receiving any PSMA-targeted therapy;
7. Requirement for steroid therapy (except for physiological replacement therapy);
8. A history of receiving immunotherapies;
9. A history of clinically significant central nervous system (CNS) diseases (either past or present at screening);

(12) A history of other untreated malignant tumors; (13) Participants with severe cardiovascular diseases; (14) Active infectious diseases; (15) Active hepatitis B or hepatitis C virus infection; (16) Active Epstein-Barr virus (EBV) or cytomegalovirus (CMV) infection (17) Intolerance or allergy to cyclophosphamide or fludarabine chemotherapeutic drugs; (18) No accessible injection sites; (19) Assessment by the investigator that the participant is unsuitable for participation in this clinical study.

主要终点：DLT · adverse events occurring within 28 days after the first infusion that are related to the study drug (definitely related, probably related, possibly related). · 28 days
次要终点：PSA50 response rate；DoPSA50（duration of PSA50 response）；DRRPSA50（durable PSA50 response rates）；TTPSAP50（time to PSA50 progression )；PSA90 response rate；DoPSA90（duration of PSA90 response）；DRRPSA90（durable PSA90 response rates)；TTPSAP90（time to PSA90 progression)

• Rapid titration dose exploration phase · EXPERIMENTAL · It is 18×10⁶ CAR-T cells, and it is planned to include 1 participant,If the participant experiences no dose-limiting toxicity (DLT) or grade 2 adverse reactions, the dose will be escalated to the 5×10⁷ CAR-T cells group for the "3+3" dose escalation; if the patient develops DLT or grade 2 adverse reactions, 2 additional participants will be enrolled, and the study will switch to the traditional "3+3" design for dose exploration.
• "3+3" dose escalation phase · EXPERIMENTAL · Dose escalation will be conducted sequentially in two dose groups: 5×10⁷ CAR-T cells and 1×10⁸ CAR-T cells. In view of the particularity of cell preparations, the actual administration dose in each dose group is allowed to have a fluctuation of ±30%. Each dose group will first enroll 3 participants. Within the same dose group, the interval between cell infusions for the first 2 participants should not be less than 14 days. During dose escalation, the interval between the infusion time of the last participant in each dose level and that of the first participant in the next dose level should be at least 28 days.If no dose-limiting toxicity (DLT) is observed in all participants within the same dose group, the dose will be escalated to the next level. If 1 case of DLT occurs, 3 additional participants will be enrolled in this dose group (with a total of 6 participants enrolled). If no new DLT occurs, the dose will be escalated to the next level.

An exploratory clinical study evaluating the safety and efficacy of ACT#001 chimeric antigen receptor T-cell (CAR-T cell) local injection in the treatment of castration-resistant prostate cancer.