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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Allogeneic dual-target antiPSMA/PSCA CAR-NK cells administered intravenously on Day 0; repeat infusion permitted only per protocol in Part B.
Lymphodepletion regimen: 30 mg/m2/day IV on Days -5 to -3 before ETB-DualNK-01 infusion.
Lymphodepletion regimen: 300 mg/m2/day IV on Days -5 to -3 before ETB-DualNK-01 infusion
Peking University Shenzhen Hospital
Shenzhen, Guangdong, China
RECRUITINGIncidence of dose-limiting toxicities (DLTs)
Time frame: 28 days
Incidence of treatment-emergent adverse events
Time frame: 12 months
Determination of maximum tolerated dose (MTD)
Time frame: 12 months
Overall response rate by RECIST 1.1
Time frame: 12 months
Radiographic progression-free survival (rPFS)
Time frame: 12 months
Duration of response
Time frame: 12 months
Overall survival
Time frame: 24 months
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