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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 36
- 试验地点
- 1
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
No masking is planned because this is an early-phase
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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
- •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 PCWG
- •Life expectancy of at least 12 weeks.
- •Ability to understand and sign informed consent and willingness to provide required blood and tissue samples.
排除标准
- •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.