An Open-Label Phase 1/2 Study of EBNK-001, an Allogeneic Natural Killer (NK) Cell Therapy Administered After Cyclophosphamide/Fludarabine Lymphodepletion With Low-Dose Interleukin-15, With or Without Pembrolizumab, in Participants With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 83
- 试验地点
- 1
- 主要终点
- Incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
研究概览
简要总结
This Phase 1/2 study evaluates the safety, tolerability, and preliminary anti-tumor activity of EBNK-001 (allogeneic NK cells) given after lymphodepleting cyclophosphamide/fludarabine (CY/FLU) and supported with low-dose IL-15, administered either alone or in combination with pembrolizumab in adults with advanced/metastatic solid tumors. The study will determine a recommended Phase 2 dose (RP2D) and explore signals of clinical activity using RECIST-based response criteria.
详细描述
EBNK-001 is an "off-the-shelf" allogeneic NK cell product intended for multi-dose administration. Participants first receive a short course of lymphodepleting chemotherapy (CY/FLU) to facilitate NK-cell expansion and persistence, followed by weekly NK-cell infusions for 3 consecutive weeks in each treatment cycle (e.g., Days 1, 8, 15). Low-dose IL-15 is administered after NK-cell infusion(s) to support NK-cell survival.
The trial includes:
Phase 1 (Dose Escalation): evaluates escalating doses of EBNK-001 to identify MTD/RP2D based on DLTs observed in the first 28 days after first NK-cell infusion (DLT window).
Phase 2 (Dose Expansion): evaluates preliminary efficacy at RP2D in selected solid tumor expansion cohorts.
Participants are followed for tumor response until progression and for survival for at least 12 months. If EBNK-001 is considered a gene-modified cell product in your program, participants may transition into a separate long-term follow-up study consistent with long-term monitoring described in NK cell therapy protocols.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years.
- •Histologically confirmed advanced/metastatic solid tumor that is relapsed/refractory after standard therapy (or no standard therapy available).
- •Measurable disease per RECIST v1.1 (or iRECIST if applicable).
- •ECOG performance status 0-1 (or 0-2 as allowed).
- •Adequate organ function (thresholds modeled on NK protocols):
- •Platelets ≥ 75,000/µL; hemoglobin ≥ 9 g/dL; ANC ≥ 1,000/µL (unsupported by growth factors/transfusions as defined).
- •eGFR ≥ 60 mL/min/1.73m².
- •AST/ALT ≤ 3× ULN.
- •Oxygen saturation ≥ 90% on room air (with PFT requirements if indicated).
- •LVEF ≥ 40% (by ECHO/MUGA/CMR).
- •If brain metastases are present, they must be stable for a defined period (example: ≥3 months) and not requiring escalating steroids.
排除标准
- •Pregnant or breastfeeding.
- •Any condition requiring systemic immunosuppression (e.g., >5 mg prednisone/day or equivalent) during dosing window (topical/inhaled may be allowed).
- •Active autoimmune disease requiring systemic immunosuppression.
- •Uncontrolled bacterial, fungal, or viral infection.
- •Receipt of investigational agent within 28 days before first study drug.
- •Live vaccine within 6 weeks prior to lymphodepletion.
- •Known HIV positivity or active hepatitis B/C with detectable viral load (protocol may allow chronic asymptomatic hepatitis depending on risk plan).
- •Known allergy to investigational product components (example: albumin/human or DMSO).
- •Any medical/social condition likely to interfere with study compliance or increase risk.
研究组 & 干预措施
EBNK-001 + IL-15 + Pembrolizumab
干预措施: EBNK-001 + IL-15 + Pembrolizumab (Biological)
结局指标
主要结局
Incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
时间窗: 30 DAYS
Incidence of Dose-Limiting Toxicities (DLTs)
时间窗: 30 DAYS
Incidence of Dose-Limiting Toxicities (DLTs)
次要结局
未报告次要终点