Dual-Target GD2/B7-H3 CAR-NK Cells for Pediatric Relapsed or Refractory Neuroblastoma

Summary

This illustrative Phase 1/Phase 2 study tests allogeneic dual-target GD2/B7-H3 (CD276) CAR-NK cells in children and young adults with relapsed or refractory neuroblastoma. After lymphodepletion, participants receive IV CAR-NK cells;Part A defines the RP2D and Part B estimates preliminary activity

Eligibility

Inclusion Criteria:

* Age 12 months to 21 years at consent/assent.
* Histologically confirmed neuroblastoma or ganglioneuroblastoma with relapsed, refractory, progressive, or persistent high-risk disease for which no curative standard option is available.
* Measurable or evaluable disease according to revised International Neuroblastoma Response Criteria (rINRC), including MIBG-avid disease, CT/MRI-evaluable soft-tissue disease, and/or bone marrow disease.
* Tumor material available for central assessment of GD2 and B7-H3 expression; at least one target must be positive.

GD2 is treated as the core target and B7-H3 as the complementary target for correlative target-prioritization analyses.

* Prior exposure to standard neuroblastoma therapy, including anti-GD2-based therapy, unless contraindicated, unavailable, or declined for a documented medical reason.
* Lansky or Karnofsky performance score \>= 50.
* Life expectancy \>= 8 weeks.
* Recovery from clinically significant acute toxicities of prior therapy and protocol-defined washout from chemotherapy, biologics, radiation, and prior cell therapy.
* Adequate organ function: hematologic, renal, hepatic, cardiac, and pulmonary function considered sufficient by protocoldefined laboratory and clinical thresholds.
* Negative pregnancy test for patients of childbearing potential and agreement to use effective contraception during the protocol-defined period.
* Written informed consent from parent/legal guardian and assent from the participant when appropriate.

Exclusion Criteria:

* Active uncontrolled infection, including bacteremia, uncontrolled viral infection, or invasive fungal disease.
* Pregnancy or breastfeeding.
* Active grade \>= 2 graft-versus-host disease, or systemic immunosuppression for treatment/prevention of graft-versushost disease within the protocol-defined washout period after prior allogeneic transplant.
* Symptomatic or unstable central nervous system disease requiring urgent medical intervention.
* Prior genetically modified cellular therapy within the protocol-defined washout window, or unresolved clinically significant toxicity from prior cell therapy.
* Active autoimmune disease requiring systemic immunosuppressive therapy.
* Clinically significant uncontrolled cardiovascular, pulmonary, hepatic, renal, or neurologic disorder that would increase study risk.
* Known hypersensitivity to fludarabine, cyclophosphamide, study-product components, or supportive-care medications required by the protocol.
* Known uncontrolled HIV infection or uncontrolled hepatitis B or C.
* Any medical, psychosocial, or logistical condition that, in the investigator's judgment, would make study participation unsafe or would impair protocol adherence.

Conditions5

Interventions3

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