CELL INTELLIGENCE · 肿瘤细胞治疗研究

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.

主要终点：Incidence of dose-limiting toxicities (DLTs) · 28 days；Incidence of treatment-emergent adverse events · 12 months；Determination of maximum tolerated dose (MTD) · 12 months
次要终点：Overall response rate by RECIST 1.1；Radiographic progression-free survival (rPFS)；Duration of response；Overall survival

• Dose Escalation · EXPERIMENTAL · Participants receive fludarabine/cyclophosphamide lymphodepletion followed by a single IV infusion of ETB-DualNK-01 at escalating dose levels. Safety during the Day 28 DLT window determines escalation.
• Dose Expansion · EXPERIMENTAL · Participants receive ETB-DualNK-01 at the selected RP2D after the same lymphodepletion regimen. One optional repeat infusion may be permitted if predefined safety criteria are met.

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.