Biomarker-Guided Allogeneic Single-Target or Dual-Target CAR-NK Cell Therapy for Advanced Solid Tumors

Официальное название

A Phase 1/2, Open-Label, Biomarker-Driven Study of Allogeneic Donor-Derived CAR-NK Cells With Antigen Selection by Tissue Biopsy and/or Liquid Biopsy Profiling in Participants With Relapsed/Refractory Advanced Solid Tumors (Single-Target vs Dual-Target Strategy)

Обзор

This Phase 1/2 study evaluates the safety, feasibility, and preliminary anti-tumor activity of allogeneic donor-derived CAR-NK cells in participants with advanced solid tumors. The CAR target antigen is selected for each participant after tumor profiling using a tissue biopsy and/or liquid biopsy. Participants will receive either a single-target or dual-target CAR-NK product based on the antigen profile.

Подробное описание

This is an open-label, biomarker-driven adoptive cell therapy study.

Screening / Target Selection (Precision Step):

Participants undergo tumor antigen profiling using:

Tissue biopsy (preferred when safely feasible), and/or Liquid biopsy (e.g., circulating tumor DNA plus circulating tumor cells/exosome protein assay, as available in the platform).

Antigen profiling determines eligibility and assigns participants to:

Single-target CAR-NK if one antigen meets positivity thresholds, or Dual-target CAR-NK if two antigens meet thresholds or if heterogeneity is suspected.

Pre-specified target menu :

TROP2, Mesothelin (MSLN), B7-H3 (CD276), HER2, EGFR, GD2, Claudin18.2, GPC3, PSMA ("Target menu" can be expanded in amendments.)

Cell Source / Manufacturing Concept:

NK cells are obtained from a healthy allogeneic donor (unrelated or partially matched per site policy).

Donor NK cells are collected by leukapheresis, activated/expanded, and genetically modified to express:

a single CAR (Arm A) or a dual CAR / dual-target construct (Arm B). Final product is cryopreserved and released after sterility/identity/potency testing.

Conditioning \& Treatment:

Participants receive lymphodepleting chemotherapy followed by CAR-NK infusion(s). Many CAR-NK solid-tumor trials use conditioning regimens such as fludarabine and cyclophosphamide before infusion.

Optional cytokine support (e.g., low-dose IL-2) may be used per protocol to support NK persistence, consistent with approaches used in some CAR-NK studies.

Follow-up:

Intensive safety monitoring during the first 28 days. Tumor imaging at protocol-defined intervals. Correlative studies including CAR-NK persistence and ctDNA dynamics.

Вмешательства

• Биопрепарат EB-SELECT Single-Target CAR-NK Cells
  Donor-derived CAR-NK cells expressing a single CAR selected from the target menu. WITH Fludarabine (IV) + Cyclophosphamide (IV), administered prior to CAR-NK infusion. Similar conditioning drugs are used in CAR-NK solid tumor trials.
• Биопрепарат Dual-Target Antigen-Selected CAR-NK
  Participants whose profiling identifies two actionable antigens, or strong evidence of antigen heterogeneity. WITH Fludarabine (IV) + Cyclophosphamide (IV), administered prior to CAR-NK infusion . Similar conditioning drugs are used in CAR-NK solid tumor trials.

Первичные конечные точки

• Incidence, type, and severity of adverse events (AEs), graded by CTCAE v5.0 [Срок оценки: 28 DAYS]
• Incidence of Dose-Limiting Toxicities (DLTs) [Срок оценки: 28 DAYS]

Вторичные конечные точки (2)

• Objective Response Rate (ORR) (RECIST 1.1) [Срок оценки: 12 months]
• Disease Control Rate (DCR) [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Age 18-75 years.
• Histologically or cytologically confirmed advanced/unresectable or metastatic solid tumor that is relapsed/refractory after standard therapy, or no standard therapy available.
• Targetable antigen positivity from the protocol target menu based on:

tissue biopsy and/or liquid biopsy platform (as defined in the lab manual).

• Arm assignment rules :
• Arm A: ≥1 antigen meets "positive" threshold
• Arm B: ≥2 antigens meet "positive" threshold
• ECOG performance status 0-1 (or 0-2 ).
• At least one measurable lesion by RECIST 1.1.
• Adequate organ function (hematologic, renal, hepatic, cardiac) within protocol-defined limits.
• Willingness to undergo blood draws and required biopsies (when medically feasible).
• Negative pregnancy test for participants of childbearing potential; agreement to effective contraception during and after study treatment.

Критерии исключения

• Prior treatment with gene-modified cellular therapy (e.g., CAR-T, CAR-NK) within a defined washout period .
• Active, uncontrolled infection requiring IV antibiotics; known uncontrolled HIV; active HBV/HCV with detectable viral load (per local policy).
• Active CNS metastases requiring escalating steroids or urgent intervention (stable treated CNS disease may be allowed ).
• Active autoimmune disease requiring systemic immunosuppression, or chronic systemic steroids above protocol threshold.
• Clinically significant cardiovascular disease (e.g., recent MI, unstable arrhythmia), uncontrolled pulmonary disease, or other serious comorbidity that increases risk.
• Major surgery or anticancer therapy too close to lymphodepletion (protocol-defined washout).
• 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

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• District One Hospital — Пекин

Идентификаторы

NCT: NCT07410494 · EB-CARNK-S002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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