Allogeneic anti-PSMA CAR‑NK cell therapy for metastatic castration‑resistant prostate cancer

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 trial will try an off‑the‑shelf CAR‑NK cell therapy that targets PSMA in men with metastatic castration‑resistant prostate cancer to see if it is safe and can shrink disease.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences (Academic / other)
• Drugs / interventions: CAR-T, chimeric antigen receptor, immunotherapy, chemotherapy
• Locations: 1 site (Beijing, 不限)
• Trial ID: NCT07298239 on ClinicalTrials.gov

What this trial studies

This is an early‑phase, interventional trial giving allogeneic anti‑PSMA CAR‑NK cells to men with PSMA‑positive metastatic castration‑resistant prostate cancer. Participants must have castrate‑level testosterone, evidence of disease progression (rising PSA or new radiographic lesions), ECOG 0–2, and expected survival of at least six months. The study will primarily monitor safety and tolerability and collect preliminary signs of anti‑tumor activity using PSA trends and radiographic assessments (RECIST and bone scans). Treatment is delivered as engineered NK cell infusions with scheduled follow‑up to watch for adverse events and response.

Who should consider this trial

Good fit: Ideal candidates are adult men with PSMA‑positive metastatic castration‑resistant prostate cancer who have progressed on standard therapies, have ECOG performance status 0–2, and an expected survival of at least six months.

Not a fit: Patients without PSMA expression, with poor performance status, very limited life expectancy, or those previously treated with other cellular therapies (as excluded) are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the therapy could provide a targeted immune option that kills PSMA‑expressing prostate cancer cells and potentially controls disease with a different side‑effect profile than existing treatments.

How similar studies have performed: CAR‑NK approaches have shown early promising safety signals in other cancers and CAR‑based PSMA targeting has had mixed early results in prostate cancer, so this is a promising but still largely unproven approach for mCRPC.

Eligibility criteria

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.

Where this trial is running

Beijing, 不限

• Cancer Hospital Chinese Academy of Medical Sciences — Beijing, 不限, China (Recruiting)

Conditions Prostate Cancer Castration-resistant Prostate Cancer