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

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Castration-Resistant Prostate Cancer (CRPC)
• Intervention / Treatment: Biological: Intraprostatic or localized lesion injection of ACT#001-PSMA CAR-T cells under transrectal ultrasound (TRUS) guidance

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • The First Affiliated Hospital of Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rapid titration dose exploration phase; 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.	Biological: Intraprostatic or localized lesion injection of ACT#001-PSMA CAR-T cells under transrectal ultrasound (TRUS) guidance; Prior to CAR-T cell infusion, subjects will receive lymphodepleting chemotherapy based on fludarabine and cyclophosphamide. Surgical method : 1)The patient is taken to the operating room, and the anesthesia method is intravenous anesthesia or local anesthesia. A digital rectal examination is performed, and the anus is dilated to accommodate three fingers. The genitals and perineum are prepared and covered in a sterile manner. An ultrasound probe is inserted into the rectum; (2) Under ultrasound guidance, CAR-T cells are injected into the prostate or localized lesions via the rectum or perineum; (3) Then, the TRUS probe is removed from the patient's rectum.
Experimental: "3+3" dose escalation phase; 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.	Biological: Intraprostatic or localized lesion injection of ACT#001-PSMA CAR-T cells under transrectal ultrasound (TRUS) guidance; Prior to CAR-T cell infusion, subjects will receive lymphodepleting chemotherapy based on fludarabine and cyclophosphamide. Surgical method : 1)The patient is taken to the operating room, and the anesthesia method is intravenous anesthesia or local anesthesia. A digital rectal examination is performed, and the anus is dilated to accommodate three fingers. The genitals and perineum are prepared and covered in a sterile manner. An ultrasound probe is inserted into the rectum; (2) Under ultrasound guidance, CAR-T cells are injected into the prostate or localized lesions via the rectum or perineum; (3) Then, the TRUS probe is removed from the patient's rectum.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSA50 response rate	The proportion of participants with a reduction of ≥50% in PSA from baseline to the lowest post-baseline PSA result, which needs to be confirmed by a second consecutive PSA assessment after at least 3 weeks.	6 months
DoPSA50（duration of PSA50 response）	The time from the date of first documented PSA50 response (subsequently confirmed) to the date of documented PSA progression per PCWG3 criteria or death from any cause in the absence of PSA progression.	6 months
DRRPSA50（durable PSA50 response rates）	The percentage of participants with a confirmed PSA50 response lasting at least 6 months, using the number of participants in the PSA evaluable set as the denominator.	6 months
TTPSAP50（time to PSA50 progression )	The time from the date of the first documented PSA50 response (subsequently confirmed) to the date of documented PSA progression per PCWG3 criteria.	6 months
PSA90 response rate	The proportion of participants with a reduction of ≥90% in PSA from baseline to the lowest post-baseline PSA result, which needs to be confirmed by a second consecutive PSA assessment after at least 3 weeks.	6 Months
DoPSA90（duration of PSA90 response）	The time from the date of first documented PSA90 response (subsequently confirmed) to the date of documented PSA progression per PCWG3 criteria or death from any cause in the absence of PSA progression.	6 months
DRRPSA90（durable PSA90 response rates)	The percentage of participants with a confirmed PSA90 response lasting at least 6 months, using the number of participants in the PSA evaluable set as the denominator.	6 months
TTPSAP90（time to PSA90 progression)	The time from the date of the first documented PSA90 response (subsequently confirmed) to the date of documented PSA progression per PCWG3 criteria.	6 months
ORR	The proportion of patients achieving complete response (CR) or partial response (PR).	6 MONTHS
DOR（Duration of Response）	The duration from the initial achievement of partial response (PR) or complete response (CR) to the occurrence of disease progression or death.	6MONTHS
DCR（Disease Control Rate）	The proportion of patients achieving complete response (CR), partial response (PR), or stable disease (SD).	6months
TTR（Time to Response）	The time from treatment initiation to the first achievement of partial response (PR) or complete response (CR).	6mohths
OS（Overall Survival）	The time from treatment initiation to death from any cause.	6 months
rPFS（Radiographic Progression-Free Survival）	The time from treatment initiation to radiologically documented disease progression or death.	6 months
mFS	The time from treatment initiation to the development of distant metastasis or death.	6 months
In vivo persistence time of CAR-T cells	The time from the infusion of ACT#001-PSMA CAR-T cells to the point when ACT#001-PSMA CAR-T cells can no longer be detected in the body (with 2 consecutive negative test results), which is detected by methods such as QPCR and flow cytometry.	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of immune cell subsets in peripheral blood	At five fixed timepoints-pre-lymphodepletion, post-lymphodepletion (pre-infusion), post-infusion (D0/D1), discharge (e.g., D7), and D28-as well as at the onset of CRS, to explore the proportion of immune cell subsets in peripheral blood	28 DAYS
The proportion of subgroups of the intestinal microbiota	At five fixed timepoints-pre-lymphodepletion, post-lymphodepletion (pre-infusion), post-infusion (D0/D1), discharge (e.g., D7), and D28-as well as at the onset of CRS to explore the the proportion of subgroups of the intestinal microbiota from stool samples	28 DAYS
The correlation between therapeutic effect and PSA level	The correlation between therapeutic effect and PSA level	6 months
The correlation between therapeutic effect and percentage of histological PSMA expression	The correlation between therapeutic effect and percentage of histological PSMA expression	6 months
The correlation between therapeutic effect and HRR mutation status	The correlation between therapeutic effect and HRR mutation status	6 months
The correlation between therapeutic effect and dMMR/MSI-H status	The correlation between therapeutic effect and dMMR/MSI-H status	6 months
The correlation between therapeutic effect and prior treatment regimens	The correlation between therapeutic effect and prior treatment regimens	6 months
The correlation between therapeutic effect and disease classification (mCRPC vs. nmCRPC)	The correlation between therapeutic effect and disease classification (mCRPC vs. nmCRPC)	6 months

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Orig Stone Biotech(Zhejiang) Co.,Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2026
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: August 23, 2025
• First Submitted That Met QC Criteria: November 20, 2025
• First Posted (Actual): November 21, 2025

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: CAR-T; CRPC
• Additional Relevant MeSH Terms: Health Services; Health Care Facilities Workforce and Services; Community Health Services; Behavioral Disciplines and Activities; Mental Health Services; Counseling
• Other Study ID Numbers: ACT#001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No