EBNK-001 Allogeneic NK Cells With Low-Dose IL-15 ± Pembrolizumab in Advanced Solid Tumors

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Биопрепарат EBNK-001 + IL-15 + Pembrolizumab
  Biological: EBNK-001 (Allogeneic NK Cells) Dose levels (example): 1×10\^8; 3×10\^8; 9×10\^8 viable cells/infusion Schedule: weekly infusions on Days 1, 8, and 15 (per cycle) Drug: Cyclophosphamide (CY) lymphodepletion: 300 mg/m² IV daily ×2 days (Cycle 1 only) Drug: Fludarabine (FLU) Example lymphodepletion: 25 mg/m² IV daily ×2 days (Cycle 1 only) Drug: Interleukin-15 (IL-15) Low-dose IL-15 given after NK cell infusion to support NK cell survival dose used in NK protocols: 6 MIU per dose Dru

Первичные конечные точки

• Incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) [Срок оценки: 30 DAYS]
• Incidence of Dose-Limiting Toxicities (DLTs) [Срок оценки: 30 DAYS]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• District One Hospital — Пекин

Идентификаторы

NCT: NCT07410676 · EB-NK-ST-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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