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

NCT07502287 | Recruiting Phase 1 DMC

• 1 other identifier: EB-CARNK-CRC-103
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

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

Keywords

pediatric neuroblastoma; CAR-NK; GD2; B7-H3; CD276; dual-targeting; relapsed/refractory; allogeneic; solid tumor immunotherapy; cell therapy; biomarkerinformed design

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicities (DLTs) after first CARNK infusion, using protocol-defined DLT criteria.

  28 days

• Incidence and severity of treatment-emergent adverse events

  Incidence and severity of treatment-emergent adverse events, including CRS and ICANS, graded using CTCAE v5.0 and ASTCT consensus criteria.

  12 months

Secondary Outcomes (4)

• Objective response rate by revised International Neuroblastoma Response Criteria (rINRC).

  12 months

• Duration of response among responders

  24 months

• Progression-free survival

  12 months

• Overall survival

  24 months

Study Arms (1)

EB-DTNB-NK

EXPERIMENTAL

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.

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

Interventions

EB-DTNB-NK BIOLOGICAL

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.

Also known as: Dual-target GD2/B7-H3 CAR-NK

EB-DTNB-NK

Fludarabine DRUG

Lymphodepleting chemotherapy administered before CAR-NK infusion according to the protocol-defined conditioning regimen.

Also known as: Flu

EB-DTNB-NK

Cyclophosphamide DRUG

Lymphodepleting chemotherapy administered before CAR-NK infusion according to the protocol-definedb conditioning regimen.

Also known as: Cy

EB-DTNB-NK

Eligibility Criteria

• Age: 12 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Biotech: lead

Study Sites (1)

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

RECRUITING

MeSH Terms

Conditions

Neuroblastoma; Ganglioneuroblastoma; Recurrence

Interventions

fludarabine; Influenza Vaccines; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Central Study Contacts

Seni S Lu, Phd

CONTACT

+86 13076790030; Seni-Lu@beijing-biotech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Masking is not used because the study is an earlyphase cell-therapy trial focused on safety, dose finding, feasibility, pharmacodynamics, and preliminary efficacy.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multicenter, open-label, biomarker-informed study with Part A (standard 3+3 dose-escalation) followed by Part B (dose expansion at the RP2D). All treated participants receive the same investigational dual-target CAR-NK product after baseline assessment of GD2 and B7-H3 expression. Biomarker analyses are prespecified to explore which antigen profile appears most suitable for later-stage development.

Study Record Dates

• First Submitted: March 25, 2026
• First Posted: March 30, 2026
• Study Start: March 2, 2026
• Primary Completion (Estimated): March 14, 2027
• Study Completion (Estimated): June 17, 2028
• Last Updated: March 30, 2026

Record last verified: 2026-03

Locations

CN (1)