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
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
36
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.
Lymphodepleting chemotherapy administered before CAR-NK infusion according to the protocol-defined conditioning regimen.
Lymphodepleting chemotherapy administered before CAR-NK infusion according to the protocol-definedb conditioning regimen.
Peking University Shenzhen Hospital
Shenzhen, Guangdong, China
RECRUITINGIncidence of dose-limiting toxicities (DLTs) after first CARNK infusion, using protocol-defined DLT criteria.
Time frame: 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.
Time frame: 12 months
Objective response rate by revised International Neuroblastoma Response Criteria (rINRC).
Time frame: 12 months
Duration of response among responders
Time frame: 24 months
Progression-free survival
Time frame: 12 months
Overall survival
Time frame: 24 months
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