Dual-target PSMA/PSCA CAR-NK Cells in Advanced Prostate Cancer

Official title

A Phase 1, Open-Label, Multicenter, Dose-Escalation and Dose-Expansion Study of ETB-DualNK-01, an Allogeneic Dual-target PSMA/PSCA CAR-NK Cell Product, in Adults With Metastatic Castration-Resistant Prostate Cancer

Overview

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

• Biological ETB-DualNK-01
  Allogeneic dual-target antiPSMA/PSCA CAR-NK cells administered intravenously on Day 0; repeat infusion permitted only per protocol in Part B.
• Drug Fludarabine
  Lymphodepletion regimen: 30 mg/m2/day IV on Days -5 to -3 before ETB-DualNK-01 infusion.
• Drug Cyclophosphamide
  Lymphodepletion regimen: 300 mg/m2/day IV on Days -5 to -3 before ETB-DualNK-01 infusion

Primary outcome measures

• Incidence 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]

Secondary outcome measures (4)

• 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]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Peking University Shenzhen Hospital — Shenzhen

Identifiers

NCT: NCT07641049 · ETB-CARNK-PSMAPSCA-004

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗