About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Single group
Treatments tested in this trial
EB-DTNB-NK
Biological/VaccineAllogeneic, 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.
Fludarabine
DrugLymphodepleting chemotherapy administered before CAR-NK infusion according to the protocol-defined conditioning regimen.
Cyclophosphamide
DrugLymphodepleting chemotherapy administered before CAR-NK infusion according to the protocol-definedb conditioning regimen.
Treatment groups
Trial outcomes
Primary outcomes
Incidence of dose-limiting toxicities (DLTs) after first CARNK infusion, using protocol-defined DLT criteria.
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.
Secondary outcomes
Objective response rate by revised International Neuroblastoma Response Criteria (rINRC).
Duration of response among responders
Progression-free survival
Overall survival
Sponsors and contacts
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