Advanced Prostate Adenocarcinoma, Metastatic Castration-resistant Prostate Cancer, PSCA-positive Prostate Cancer, PSMA-Positive Progressive Metastatic Castration-Resistant Prostate Cancer
Conditions
Keywords
CAR-NK, dual-target, PSMA, PSCA, mCRPC, metastatic prostate cancer, cell therapy, immunotherapy, dose escalation, dose expansion
Brief summary
This example Phase 1 study is designed to evaluate the safety, tolerability, feasibility, and preliminary anti-tumor activity of ETB-DualNK-01, an allogeneic dual-target PSMA/PSCA CAR-NK cell therapy, in adults with metastatic castration-resistant prostate cancer (mCRPC). Part A uses dose escalation to determine the maximum tolerated dose and/or recommended Phase 2 dose. Part B expands at the selected dose in biomarkerconfirmed disease.
Detailed description
PSMA is the most clinically validated cell-surface target in advanced prostate cancer, while PSCA provides a complementary prostate-associated antigen with direct phase 1 cell-therapy precedent in mCRPC. Dual recognition is intended to improve tumor coverage and reduce the risk of antigen escape across heterogeneous metastatic lesions. Eligible participants will undergo screening to confirm metastatic CRPC, document PSMA and/or PSCA expression, establish baseline PSA and imaging status, and verify adequate organ function. Ongoing androgen deprivation therapy will be maintained to preserve castrate testosterone levels throughout study treatment. Participants will receive lymphodepletion with fludarabine and cyclophosphamide followed by intravenous ETBDualNK-01 on Day 0. In the dose-expansion part, one optional repeat infusion may be allowed after protocoldefined safety review to improve NK-cell persistence. Imaging and PSA assessments will occur every 8 weeks during the first 6 months and every 12 weeks thereafter.
Interventions
BIOLOGICALETB-DualNK-01
Allogeneic dual-target antiPSMA/PSCA CAR-NK cells administered intravenously on Day 0; repeat infusion permitted only per protocol in Part B.
DRUGFludarabine
Lymphodepletion regimen: 30 mg/m2/day IV on Days -5 to -3 before ETB-DualNK-01 infusion.
DRUGCyclophosphamide
Lymphodepletion regimen: 300 mg/m2/day IV on Days -5 to -3 before ETB-DualNK-01 infusion
Sponsors
Beijing Biotech
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
No masking is planned because this is an early-phase
Intervention model description
Part A: 3+3 dose-escalation of ETB-DualNK-01 after fludarabine/cyclophosphamide lymphodepletion. Part B:dose-expansion at the selected RP2D in biomarkerconfirmed disease.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male participant age 18 years or older. * Histologically or cytologically confirmed prostate adenocarcinoma with metastatic castration-resistant disease. * Disease progression by PCWG3 while maintaining castrate testosterone (\<50 ng/dL) with ongoing androgen deprivation therapy or prior orchiectomy. * Documented PSMA and/or PSCA expression by a validated tumor assay; PSMA PET may support target confirmation when applicable. * Prior progression on at least one androgen receptor pathway inhibitor such as abiraterone, enzalutamide, apalutamide, or darolutamide; prior taxane, PARP inhibitor, radioligand therapy, or checkpoint inhibitor is allowed. * ECOG performance status 0 or 1. * Adequate hematologic, renal, hepatic, cardiac, and pulmonary function per protocol laboratory thresholds. * At least one measurable lesion by RECIST 1.1 or evaluable bone-predominant disease by PCWG3. * Life expectancy of at least 12 weeks. * Ability to understand and sign informed consent and willingness to provide required blood and tissue samples.
Exclusion criteria
* Active central nervous system metastases or leptomeningeal disease. * Dominant small-cell or neuroendocrine prostate cancer histology. * Prior gene-modified cellular therapy within 6 months before lymphodepletion, or prior allogeneic transplant requiring ongoing systemic immunosuppression. * Active autoimmune disease requiring systemic treatment or chronic immunosuppression; systemic corticosteroid use greater than 10 mg prednisone equivalent daily within 7 days of lymphodepletion. * Uncontrolled infection, including uncontrolled hepatitis B, hepatitis C, or HIV infection. * Clinically significant cardiovascular disease, symptomatic arrhythmia, recent myocardial infarction, or uncontrolled heart failure. * Unresolved grade 2 or higher toxicity from prior anticancer therapy, except alopecia, stable endocrinopathy, or other protocol-approved exceptions. * Another active malignancy requiring systemic treatment. * Any medical, psychiatric, or laboratory abnormality that, in the investigator's judgment, would increase risk or interfere with study interpretation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of dose-limiting toxicities (DLTs) | 28 days |
| Incidence of treatment-emergent adverse events | 12 months |
| Determination of maximum tolerated dose (MTD) | 12 months |
Secondary
| Measure | Time frame |
|---|---|
| Overall response rate by RECIST 1.1 | 12 months |
| Radiographic progression-free survival (rPFS) | 12 months |
| Duration of response | 12 months |
| Overall survival | 24 months |
Countries
China
Contacts
CONTACTSeni S Lu, Phd
Outcome results
None listed