An Exploratory Clinical Study Evaluating the Safety and Efficacy of Allogeneic CAR-NK Cell Therapy for Metastatic Castration-resistant Prostate Cancer (mCRPC)

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer Castration-resistant Prostate Cancer
• Intervention / Treatment: Biological: anti-PSMA CAR-NK

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • 不限
    • Beijing, 不限, China, 100000
      • Recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences
      • Contact: sujun Han Han; Phone Number: 010-67781331; Email: cancergcp@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group	Biological: anti-PSMA CAR-NK; Targeting PSMA CAR-NK cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of treatment related adverse events as assessed by CTCAE v5.0	Defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment	Baseline to 1 year post infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS) after Anti-PSMA CAR NK Cell infusion	Survival time of patients	Baseline to 1 year post infusion
The pharmacokinetic analysis of Anti-PSMA CAR-NK Cell	Changes in the number of CD56+/ CD3 Anti-PSMA CAR-NK Cell in peripheral blood over time	Day-2-Day-1、Day0、Day2、Day7、Day9、Day14、Day16、Day21、Day28、Day60 and Day90 post infusion
The pharmacodynamics analysis of Anti-PSMA CAR NK Cell	Changes of total prostate specific antigen (tPSA) and free prostate specific antigen (fPSA) in peripheral blood	Baseline to infusion date、Day0、Day1、Day2、Day7、Day8、Day9、Day14、Day15、Day16、Day21、Day28、Day60、Day90、Day120、Day180、Day270 and Day360
The proportion of patients with a decrease in PSA levels from baseline	PSA response rate	Baseline toDay0、Day1、Day2、Day7、Day8、Day9、Day14、Day15、Day16、Day21、Day28、Day60、Day90、Day120、Day180、Day270 and Day360 post infusion
Time to clinical progression	The time from baseline to the appearance of increased PSA levels or imaging progression.	Baseline to Day28、Day90、Day180、Day270 and Day360 post infusion

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: November 24, 2025
• First Submitted That Met QC Criteria: December 17, 2025
• First Posted (Actual): December 23, 2025

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 25/216-0216

Drug and device information, study documents

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