Target-Selected CAR-NK Cells (CD30, CD5, or Mesothelin) for Relapsed/Refractory B2 Thymoma or Thymic Carcinoma

Официальное название

A Phase 1/2, Open-Label, Target-Selected Study of Allogeneic CAR-NK Cells Directed to CD30, CD5, or Mesothelin in Patients With Relapsed/Refractory B2 Thymoma or Thymic Carcinoma

Обзор

This Phase 1/2 study evaluates the safety, tolerability, and preliminary efficacy of target-selected CAR-natural killer (CAR-NK) cells in adults with relapsed or refractory B2 thymoma or thymic carcinoma. Participants undergo centralized tumor antigen assessment (CD30, CD5, and mesothelin). Based on the dominant and clinically actionable antigen expression profile, each participant is assigned to one of three parallel cohorts (CD30-CAR-NK, CD5-CAR-NK, or mesothelin-CAR-NK). All cohorts use the same lymphodepleting conditioning regimen followed by CAR-NK infusion(s).

Подробное описание

This is a first-in-indication, open-label, non-randomized, multi-center Phase 1/2 study with biomarker-driven cohort assignment. Phase 1 (dose escalation): Within each target cohort, a standard 3+3 dose-escalation design evaluates up to three dose levels of the assigned CAR-NK product to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Dose-limiting toxicities (DLTs) are assessed from Day 0 through Day 28 after the first CAR-NK infusion. Phase 2 (dose expansion): After an RP2D is identified in a cohort, an expansion stage enrolls additional participants in that cohort to further characterize safety and estimate preliminary antitumor activity. CAR-NK product: Off-the-shelf, allogeneic cord blood-derived NK cells are genetically modified to express a single-target CAR (anti-CD30, anti-CD5, or anti-mesothelin). The construct includes an IL-15 support element to enhance persistence and an inducible caspase-9 (iCasp9) safety switch for rapid elimination of CAR-NK cells if clinically indicated. Correlative studies: Serial blood and (when feasible) tumor sampling will evaluate CAR-NK persistence, immune activation markers, cytokines, tumor antigen modulation, and exploratory biomarkers of response and resistance. Long-term follow-up: Participants will be followed for delayed adverse events and survival; participants receiving gene-modified cells will also be invited to long-term follow-up consistent with applicable gene therapy guidance.

Вмешательства

• Препарат Cyclophosphamide
  lymphodepletion
• Препарат Fludarabine
  lymphodepletion
• Биопрепарат EB-CAR30-NK
  CD30-targeted allogeneic CAR-NK cells
• Биопрепарат EB-CAR5-NK
  CD5-targeted allogeneic CAR-NK cells
• Биопрепарат EB-CARMSLN-NK
  Mesothelin-targeted allogeneic CAR-NK cells
• Препарат Rimiducid (AP1903)
  ctivate the iCasp9 safety switch if clinically indicated

Первичные конечные точки

• Incidence of Dose-Limiting Toxicities (DLTs) [Срок оценки: 28 Days]
• Recommended Phase 2 Dose [Срок оценки: 28 Days]

Вторичные конечные точки (2)

• Objective Response Rate [Срок оценки: 12 months]
• Disease Control Rate [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Age 18 to 75 years at the time of consent.
• Histologically confirmed B2 thymoma or thymic carcinoma that is unresectable, metastatic, or recurrent.
• Relapsed or refractory after at least 1 prior systemic therapy (including a platinum-based regimen for thymic carcinoma when appropriate) or no standard curative option available.
• Tumor antigen positivity for at least one of the following by central laboratory assessment: CD30, CD5, or mesothelin. Cohort assignment is based on the dominant target (pre-specified algorithm) and feasibility of manufacturing/availability.
• Measurable disease per RECIST v1.1 (or evaluable disease if measurable disease is not feasible; to be specified).
• ECOG performance status 0-1 (0-2 may be permitted in expansion at investigator discretion).
• Adequate organ function: ANC ≥ 1.0 x 10\^9/L, platelets ≥ 75 x 10\^9/L, hemoglobin ≥ 8 g/dL (transfusions allowed), AST/ALT ≤ 3 x ULN (≤ 5 x ULN with liver involvement), total bilirubin ≤ 1.5 x ULN (except Gilbert's), creatinine clearance ≥ 50 mL/min.
• Negative pregnancy test for participants of childbearing potential; agreement to use effective contraception.
• Ability to understand and sign informed consent.

Критерии исключения

• Active central nervous system involvement by malignancy requiring immediate therapy.
• Prior gene-modified cellular therapy (e.g., CAR-T, CAR-NK) within 90 days or unresolved ≥Grade 2 toxicity from prior cellular therapy.
• Uncontrolled infection, including active tuberculosis, or uncontrolled hepatitis B or C infection; known uncontrolled HIV infection.
• Clinically significant autoimmune disease requiring systemic immunosuppression (e.g., >10 mg/day prednisone equivalent) within 14 days of conditioning, except for stable endocrine replacement.
• Prior allogeneic hematopoietic stem cell transplant with active graft-versus-host disease or ongoing immunosuppression.
• Significant cardiovascular disease (e.g., NYHA class III/IV heart failure, recent myocardial infarction), uncontrolled arrhythmia, or QTc prolongation felt to increase risk.
• Pregnancy or breastfeeding.
• Concurrent participation in another interventional trial with an investigational anticancer agent within 21 days (washout required).
• Any condition that, in the investigator's judgment, would interfere with safe participation or interpretation of results.

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

• Peking University Shenzhen Hospital — Шэньчжэнь

Идентификаторы

NCT: NCT07598955 · EB-CARNK-THYM-009

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗