NCT07502287

Dual-Target GD2/B7-H3 CAR-NK Cells for Pediatric 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

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Sponsor: Beijing Biotech · Industry
• Sex: All
• Age: 12 Months – 21 Years
• Healthy volunteers: Not accepted

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

Detailed 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.

Conditions

• Relapsed Neuroblastoma
• Refractory Neuroblastoma
• High-Risk Neuroblastoma
• Ganglioneuroblastoma

Interventions

Type	Name	Description
BIOLOGICAL	EB-DTNB-NK	Allogeneic, cord blood-derived NK cells engineered with a dual-target CAR recognizing GD2 and B7-H3 (CD276), with IL-15 support and an inducible safety switch; administered intravenously on Day 0 with optional repeat dosing on Days 7 and 14 if tolerated.
DRUG	Fludarabine	Lymphodepleting chemotherapy administered before CAR-NK infusion according to the protocol-defined conditioning regimen.
DRUG	Cyclophosphamide	Lymphodepleting chemotherapy administered before CAR-NK infusion according to the protocol-definedb conditioning regimen.

Timeline

• Start date: 2026-03-02
• Primary completion: 2027-03-14
• Completion: 2028-06-17
• First posted: 2026-03-30
• Last updated: 2026-03-30

Locations

1 site across 1 country: China