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

Beijing Biotech

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: High-Risk Neuroblastoma; Refractory Neuroblastoma; Relapsed Neuroblastoma; Ganglioneuroblastoma

Treatments: Drug: Cyclophosphamide; Biological: EB-DTNB-NK; Drug: Fludarabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT07502287

EB-CARNK-CRC-103

Details and patient eligibility

About

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

Full description

The investigational product in this example is a cord blood-derived allogeneic NK-cell therapy engineered to express a dual-target CAR recognizing GD2 and B7-H3, supported by IL-15 to improve short-term persistence and equipped with an inducible safety switch. The study is designed as a multicenter Phase 1/Phase 2 protocol: Part A uses a standard 3+3 dose-escalation approach across predefined dose levels, and Part B expands at the RP2D in a biomarker-characterized population. All participants undergo central review of tumor tissue or marrow for GD2 and B7-H3 expression before treatment. Patients receive protocol-defined lymphodepletion followed by CAR-NK infusion on Day 0, with optional additional infusions on Days 7 and 14 if there is no dose-limiting toxicity (DLT), uncontrolled cytokine release syndrome (CRS), or rapid progression. Formal disease assessment uses revised International Neuroblastoma Response Criteria (rINRC). Correlative studies assess CAR-NK expansion and persistence, cytokine kinetics, tumor-response associations with antigen density, and whether future development should remain dualtarget or shift toward a GD2-dominant or B7-H3-enriched strategy. Long-term follow-up for gene-modified cellular therapy is planned per local regulatory requirements.

Enrollment: 36 estimated patients

Sex: All

Ages: 12 months to 21 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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36 participants in 1 patient group

EB-DTNB-NK

Experimental group

Description:

Participants receive protocol-defined fludarabine/cyclophosphamide lymphodepletion followed by intravenous allogeneic dual-target GD2/B7-H3 CAR-NK cells on Day 0 at the assigned dose level or RP2D. Additional doses on Days 7 and 14 are permitted if predefined safety criteria are met and there is no prohibitive toxicity or rapid progression.

Treatment:

Drug: Fludarabine

Biological: EB-DTNB-NK

Drug: Cyclophosphamide