Phase 1/2 Study of EB-NK-301 (Allogeneic TROP2-CAR NK Cells) in Advanced TROP2-Expressing Solid Tumors

Официальное название

A Phase 1/2, Open-Label, Dose-Escalation and Dose-Expansion Study Evaluating the Safety, Tolerability, and Preliminary Anti-tumor Activity of EB-NK-301 (Allogeneic TROP2-Targeted CAR NK Cells) Following Lymphodepleting Chemotherapy in Adults With Advanced or Metastatic TROP2-Expressing Solid Tumors

Обзор

study evaluates EB-NK-301, an investigational off-the-shelf allogeneic CAR-NK cell product targeting TROP2, in adults with advanced or metastatic solid tumors that express TROP2 and have progressed after standard therapy. The primary goals are to assess safety and tolerability, identify dose-limiting toxicities (DLTs), and determine a recommended Phase 2 dose (RP2D). Secondary goals include preliminary anti-tumor activity, persistence of infused CAR-NK cells, and exploratory immune biomarkers.

Подробное описание

Study Overview: The study includes two parts. Part A (dose escalation) uses a standard dose-escalation design to evaluate multiple dose levels of EB-NK-301 after lymphodepleting chemotherapy. Part B (dose expansion) enrolls additional participants at the selected RP2D to further characterize safety and to estimate preliminary efficacy within selected tumor-type cohorts.

Treatment Plan: Participants receive lymphodepleting chemotherapy (fludarabine and cyclophosphamide) followed by intravenous EB-NK-301 infusions. Participants are monitored closely for cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infusion reactions, and other adverse events.

Assessments: Tumor imaging is performed every 8 weeks during the first 12 months, then every 12 weeks as clinically indicated. Blood samples are collected to assess CAR-NK cell persistence, cytokines, and other immune biomarkers.

Follow-up: Participants are followed for safety and survival for up to 24 months after first infusion.

Вмешательства

• Биопрепарат EB-NK-301
  Investigational allogeneic CAR-NK cell product targeting TROP2, administered by intravenous infusion.
• Препарат Fludarabine
  Lymphodepleting chemotherapy administered prior to EB-NK-301 infusion to facilitate immune cell engraftment and persistence.

Первичные конечные точки

• Incidence of dose-limiting toxicities (DLTs) (CTCAE v5.0) [Срок оценки: 28 days]
• Incidence and severity of treatment-emergent adverse events (AEs) [Срок оценки: 12 months]
• Recommended Phase 2 dose (RP2D) of EB-NK-301 [Срок оценки: 6 months]

Вторичные конечные точки (3)

• Objective response rate (ORR) per RECIST 1.1 [Срок оценки: 12 months]
• Duration of response (DoR) [Срок оценки: 24 months]
• Overall survival (OS) [Срок оценки: 24 months]

Критерии участия

Критерии включения

• Age 18 to 75 years at the time of informed consent.
• Histologically or cytologically confirmed advanced or metastatic solid tumor with documented TROP2 expression (per local testing or central confirmation).
• Disease progression on, intolerance to, or ineligibility for available standard therapy.
• At least one measurable lesion per RECIST 1.1.
• ECOG performance status 0 to 1.
• Adequate organ function (hematologic, renal, hepatic) within protocol-defined limits.
• Life expectancy ≥ 12 weeks.
• Willingness to use effective contraception during study participation and for a protocol-defined period after last infusion (if of childbearing potential).
• Ability to understand and willingness to sign written informed consent.

Критерии исключения

• Active central nervous system (CNS) metastases or leptomeningeal disease (unless treated and clinically stable for ≥ 4 weeks).
• Prior allogeneic hematopoietic stem cell transplant or solid organ transplant.
• Uncontrolled active infection, including uncontrolled hepatitis B, hepatitis C, or HIV infection.
• Active autoimmune disease requiring systemic immunosuppression.
• Clinically significant cardiovascular disease (e.g., recent myocardial infarction or stroke within 6 months, uncontrolled arrhythmia).
• Receipt of another investigational agent within 2 weeks (or 5 half-lives, whichever is longer) prior to lymphodepleting chemotherapy.
• Prior gene-modified cellular therapy within 3 months prior to enrollment.
• Systemic corticosteroid therapy > 10 mg/day prednisone equivalent within 7 days prior to lymphodepletion (excluding physiologic replacement).
• Pregnant or breastfeeding.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Peking University Shenzhen Hospital — Шэньчжэнь

Идентификаторы

NCT: NCT07589530 · EB-NK-SOLID-019

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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