Dual-target GD2 and B7-H3 CAR-NK therapy for children and young adults with relapsed or refractory neuroblastoma

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase 1/2 program uses cord blood–derived allogeneic NK cells engineered with a dual-target CAR recognizing GD2 and B7-H3, supported by IL-15 and an inducible safety switch to improve short-term persistence and control. Part A uses a standard 3+3 dose-escalation to define the recommended phase 2 dose (RP2D), and Part B expands at the RP2D in a biomarker-characterized population. Participants undergo lymphodepletion followed by IV CAR-NK infusion on Day 0 with optional additional infusions on Days 7 and 14 if safety allows, and disease response is measured by revised International Neuroblastoma Response Criteria. Correlative studies include central antigen testing, CAR-NK expansion/persistence, cytokine kinetics, and tumor antigen–response associations, with long-term follow-up per local gene-modified cell therapy requirements.

Why it matters

Who can join: the full rules

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.

Where it's running

• Peking University Shenzhen Hospital
  Shenzhen, Guangdong, China Recruiting

Study contacts

• Study coordinator: Seni S Lu, Phd
• Email: Seni-Lu@beijing-biotech.com
• Phone: +86 13076790030

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.