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

A Phase 1/Phase 2, Open-Label Study of BiomarkerInformed, Allogeneic Dual-Target GD2/B7-H3 (CD276) CAR-NK Cells in Children and Young Adults With Relapsed or Refractory Neuroblastoma

This trial tries an off-the-shelf CAR-NK cell treatment that targets GD2 and B7-H3 for children and young adults whose high-risk neuroblastoma has returned or not responded to prior therapy.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 12 Months to 21 Years
• Sex: All
• Sponsor: Beijing Biotech (Industry-sponsored)
• Drugs / interventions: chemotherapy, radiation, cyclophosphamide, fludarabine
• Locations: 1 site (Shenzhen, Guangdong)
• Trial ID: NCT07502287 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Ideal candidates are patients aged 12 months to 21 years with relapsed, refractory, progressive, or persistent high-risk neuroblastoma or ganglioneuroblastoma who have measurable or evaluable disease, available tumor/marrow for GD2 and B7-H3 testing, and at least one target positive.

Not a fit: Patients whose tumors lack both GD2 and B7-H3 expression, who have very poor performance status, significant organ dysfunction, or rapidly progressive disease unlikely to tolerate lymphodepletion are unlikely to benefit.

Why it matters

Potential benefit: If successful, this approach could offer an off-the-shelf cellular therapy that induces remissions in children and young adults with relapsed or refractory neuroblastoma, including some who received prior anti-GD2 therapy.

How similar studies have performed: While allogeneic CAR-NK products and single-target anti-GD2 immunotherapies have shown early signs of safety and activity in small studies, a dual-target GD2/B7-H3 CAR-NK approach remains largely untested in humans.

Eligibility criteria

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 this trial is running

Shenzhen, Guangdong

• Peking University Shenzhen Hospital — Shenzhen, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Seni S Lu, Phd

Conditions Relapsed Neuroblastoma; Refractory Neuroblastoma; High-Risk Neuroblastoma; Ganglioneuroblastoma; pediatric neuroblastoma; CAR-NK; GD2; B7-H3