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

Clinical Study on the Safety and Efficacy of Anti-PSMA CAR NK Cells in Patients With Metastatic Castration-resistant Prostate Cancer (mCRPC)

This trial tests an off-the-shelf CAR-NK cell therapy that targets PSMA to see if it is safe and helps men with metastatic castration-resistant prostate cancer.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences (other)
• Drugs / interventions: CAR-T, chimeric antigen receptor, immunotherapy
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07156045 on ClinicalTrials.gov

What this trial studies

This is an early-phase I, single-center study of an allogeneic anti-PSMA CAR-NK cell injection given to patients with PSMA-positive metastatic castration-resistant prostate cancer. The primary goals are to characterize safety and tolerability and to look for preliminary signs of anti-tumor activity. Eligible patients must have castrate-level testosterone, documented disease progression by rising PSA, new bone lesions, or measurable metastases, and an expected survival of at least six months. Treatment and follow-up are conducted at the Cancer Hospital, Chinese Academy of Medical Sciences in Beijing.

Who should consider this trial

Good fit: Men with metastatic castration-resistant prostate cancer whose tumors express PSMA, who have castrate testosterone levels, documented progression, and an expected survival of at least six months are the intended participants.

Not a fit: Patients without PSMA expression, with poor performance status, very limited life expectancy, or serious uncontrolled comorbidities are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the therapy could offer a new targeted cell-based treatment option for men with PSMA-positive mCRPC.

How similar studies have performed: While PSMA-targeted cellular therapies have shown early signals in other trials, allogeneic CAR-NK therapy for mCRPC is largely novel and not yet proven in clinical practice.

Eligibility criteria

Inclusion Criteria:

To enter the trial, subjects had to meet all of the following eligibility criteria:

1. diagnosed metastatic castration-resistant prostate cancer (mCRPC);
2. Castration level of serum testosterone (\< 50 ng/dL or \< 1.7 nmol/L);
3. Positive expression of PSMA;
4. According to the definition of CRPC in the Guidelines for the Diagnosis and Treatment of Prostate Cancer (2022 edition), the disease still progresses after castration and meets any of the following criteria:

   A.According to the increase in PSA level, there should be 3 consecutive increases in PSA at least 1 week apart (the increase in PSA is more than 50% of the minimum value, and PSA \> 2 ng/mL); B.Progression of bone disease as defined by PCWG3, defined as the presence of 2 or more new lesions on bone scan; C.CT or MRI results suggested measurable metastasis (lymph node short diameter \> 15 mm was defined as lymph node metastasis as assessed by RECIST 1.1);
5. Expected survival time ≥6 months;
6. Toxicity of any previous treatment had recovered to ≤ grade 1 at the time of enrollment (except hair loss and hearing loss);
7. ECOG score of patients 0-2;
8. Patients voluntarily participated and signed the informed consent, and followed the trial treatment plan and visit plan.

Exclusion Criteria:

Subjects who meet one of the following conditions will not be enrolled in the trial:

1. Previous recipients of other cell therapy products, such as dendritic cells (DC), multiple cytokine-induced killer cells (CIK), T cells, natural killer cells (NK), chimeric antigen receptor T-cell immunotherapy (CAR-T), etc.;
2. Patients with a history of biological macromolecule drug allergy;
3. Abnormal function of major organs:

   A. 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×ULN (≥5×ULN for liver metastases); C. Renal function: serum creatinine (Cr) ≥1.5×ULN; D. Prothrombin time (PT) \> 15 s, activated partial thrombin time (APTT) was prolonged or shortened by more than 10 s (normal reference value 23 s-37 s), or international normalized ratio (INR) \> 1.7; E. Pulmonary function: Severe respiratory diseases (active pulmonary tuberculosis, chronic obstructive pulmonary disease, interstitial lung disease, etc.)
4. Previous treatment with any PSMA-targeted therapy;
5. active autoimmune diseases (including connective tissue disease, uveitis, sarcoidosis, inflammatory bowel disease, or multiple sclerosis) or need long-term immunosuppressive therapy of severe autoimmune disease (screening clinic within six weeks before any immunosuppressive therapy), or by the researchers determine in 3 months will be recurrence of subjects;
6. have had other malignancies other than prostate cancer (other than basal or squamous cell skin cancer) in the past 5 years that are currently clinically significant and require intervention;
7. Any active (viral, bacterial, fungal) infection currently being treated or any infection requiring intravenous antibiotics for 7 or more days or intervals during the past 6 weeks or any active infection requiring oral antibiotics during the past 1 week;
8. untreated chronic active hepatitis B, or chronic hepatitis B virus carriers with HBV DNA≥1000 copies /mL, or active hepatitis C patients;
9. Patients who have participated in other clinical trials and used study drugs within 3 months;
10. Effective contraceptive measures cannot be adopted ;
11. In the opinion of the investigator, there are other factors that are not suitable for inclusion or affect the participant's participation or completion of the study.

Where this trial is running

Beijing, Beijing Municipality

• Cancer Hospital Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China (RECRUITING)

Conditions: Prostate Cancer Castration-resistant Prostate Cancer