A Clinical Study Evaluating the Safety and Efficacy of Local Injection of ACT#001 Chimeric Antigen Receptor T Cells in the Treatment of Castration-Resistant Prostate Cancer

Chimeric Antigen Receptor (CAR) T cells are genetically engineered T cells that can express the introduced CAR gene, which contains signaling molecules such as antigen recognition fragments, T cell receptor activation molecules, and co-stimulatory signals. Currently, in the field of hematological tumors, CD19-targeted CAR-T cells have been clinically proven to effectively treat B-cell malignancies. The US FDA has approved their use for treating relapsed or refractory CD19-positive B-cell malignancies, with favorable therapeutic effects. However, significant challenges remain before CAR-T therapy can be widely applied to solid tumor treatment. For example, the non-specific targeting of CAR-T cells to normal/non-malignant tissues ("on-target, off-tumor toxicity") can be fatal. In fact, off-tumor toxicity to the lungs, cerebral gray matter, and cardiac muscle has resulted in multiple deaths.

Prostate-specific membrane antigen (PSMA) is a surface antigen highly expressed in prostate cancer. Over 98% of lymph node metastases and almost all bone metastases in patients with castration-resistant prostate cancer (CRPC) highly express PSMA, making it an ideal target for prostate cancer treatment. We have developed a thermally activated and regulated FB-PSMA CAR-T cell targeting the prostate cancer antigen PSMA. In vitro, heating at 43°C can activate CAR expression without impairing cell function. After injection into the tumor site, PSMA-expressing prostate cancer cells can activate FB-PSMA CAR-T cells and, through a feedback mechanism, increase the expression level of CAR molecules, thereby enhancing the tumor-killing effect. Once tumor elimination is completed, CAR molecules will gradually degrade to provide a higher level of safety. In a mouse model of prostate cancer xenografts, FB-PSMA CAR-T cells have demonstrated significant anti-tumor effects and good safety.

Based on the above background, we plan to conduct this clinical trial, aiming to explore a new immunotherapeutic approach that can effectively control prostate cancer while maximizing the preservation of urogenital function and the control of oligometastases, thereby addressing the unmet needs in the current treatment of local prostate cancer. We hope that through this study, we can provide a safer and more effective treatment option for prostate cancer patients, while opening up new possibilities for future cancer treatment. This study is designed to evaluate the safety and efficacy of local injection of ACT#001 chimeric antigen receptor T cells (ACT#001-PSMA CAR-T) in the treatment of castration-resistant prostate cancer.

• PSA50 response rate [Срок оценки: 6 months]
• DoPSA50（duration of PSA50 response） [Срок оценки: 6 months]
• DRRPSA50（durable PSA50 response rates） [Срок оценки: 6 months]
• TTPSAP50（time to PSA50 progression ) [Срок оценки: 6 months]
• PSA90 response rate [Срок оценки: 6 Months]
• DoPSA90（duration of PSA90 response） [Срок оценки: 6 months]
• DRRPSA90（durable PSA90 response rates) [Срок оценки: 6 months]
• TTPSAP90（time to PSA90 progression) [Срок оценки: 6 months]
• ORR [Срок оценки: 6 MONTHS]
• DOR（Duration of Response） [Срок оценки: 6MONTHS]
• DCR（Disease Control Rate） [Срок оценки: 6months]
• TTR（Time to Response） [Срок оценки: 6mohths]