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

14 de mayo de 2026 actualizado por: Beijing Biotech

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

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).

Descripción general del estudio

Descripción detallada

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.

Tipo de estudio

Intervencionista

Inscripción (Estimado)

36

Fase

  • Fase 2
  • Fase 1

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Estudio Contacto

Ubicaciones de estudio

    • Guangdong
      • Shenzhen, Guangdong, Porcelana, 518036
        • Reclutamiento
        • Peking University Shenzhen Hospital
        • Contacto:

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

  • Adulto
  • Adulto Mayor

Acepta Voluntarios Saludables

No

Descripción

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: No aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Cohort A: CD30-CAR-NK

Lymphodepleting chemotherapy: cyclophosphamide + fludarabine (Days -5 to

-3), followed by CAR-NK infusion on Day 0. A second infusion on Day 7 may be permitted at investigator discretion in Phase 2 if no ≥Grade 3 treatment-related toxicity is observed and product is available.

agotamiento de linfocitos
agotamiento de linfocitos
CD30-targeted allogeneic CAR-NK cells
CD5-targeted allogeneic CAR-NK cells
Mesothelin-targeted allogeneic CAR-NK cells
ctivate the iCasp9 safety switch if clinically indicated
Experimental: Cohort B: CD5-CAR-NK

Lymphodepleting chemotherapy: cyclophosphamide + fludarabine (Days -5 to

-3), followed by CAR-NK infusion on Day 0. A second infusion on Day 7 may be permitted at investigator discretion in Phase 2 if no ≥Grade 3 treatment-related toxicity is observed and product is available.

agotamiento de linfocitos
agotamiento de linfocitos
CD30-targeted allogeneic CAR-NK cells
CD5-targeted allogeneic CAR-NK cells
Mesothelin-targeted allogeneic CAR-NK cells
ctivate the iCasp9 safety switch if clinically indicated
Experimental: Cohort C: Mesothelin-CAR-NK

Lymphodepleting chemotherapy: cyclophosphamide + fludarabine (Days -5 to

-3), followed by CAR-NK infusion on Day 0. A second infusion on Day 7 may be permitted at investigator discretion in Phase 2 if no ≥Grade 3 treatment-related toxicity is observed and product is available.

agotamiento de linfocitos
agotamiento de linfocitos
CD30-targeted allogeneic CAR-NK cells
CD5-targeted allogeneic CAR-NK cells
Mesothelin-targeted allogeneic CAR-NK cells
ctivate the iCasp9 safety switch if clinically indicated

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Incidence of Dose-Limiting Toxicities (DLTs)
Periodo de tiempo: 28 Days
DLTs as defined in protocol, assessed during the DLT window after the first CAR-NK infusion. Includes severe infusion-related toxicity, Grade >=3 organ toxicity attributable to CAR-NK cells, severe CRS or neurotoxicity, and treatment-related death.
28 Days
Recommended Phase 2 Dose
Periodo de tiempo: 28 Days
Determined separately for each cohort based on DLTs, overall safety, and pharmacodynamic data
28 Days

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Objective Response Rate
Periodo de tiempo: 12 months
Proportion of participants with complete response (CR) or partial response (PR) per RECIST v1.1 (or modified criteria appropriate for thymic tumors) in each cohort.
12 months
Disease Control Rate
Periodo de tiempo: 12 months
Proportion of participants with CR, PR, or stable disease
12 months

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

2 de marzo de 2026

Finalización primaria (Estimado)

14 de junio de 2027

Finalización del estudio (Estimado)

17 de abril de 2028

Fechas de registro del estudio

Enviado por primera vez

14 de mayo de 2026

Primero enviado que cumplió con los criterios de control de calidad

14 de mayo de 2026

Publicado por primera vez (Actual)

20 de mayo de 2026

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

20 de mayo de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

14 de mayo de 2026

Última verificación

1 de mayo de 2026

Más información

Términos relacionados con este estudio

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

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