Phase 1 177Lu-DTPA-omburtamab compartmental radioimmunotherapy targets B7-H3 (CD276)

This Phase 1, dose-escalation compartmental radioimmunotherapy (cRIT) study tests intrathecal/intraventricular delivery of 177Lu-DTPA-omburtamab, a B7-H3 (CD276)-targeting murine monoclonal antibody chelated with DTPA and radiolabeled with lutetium-177 (beta-emitting radionuclide) to deliver targeted radiation within the CNS. The trial is run by Memorial Sloan Kettering Cancer Center (MSK) and focuses on defining safety, tolerability, dosimetry/PK, and a recommended dose across planned activity levels (25, 50, 75, 100 mCi). Eligible patients are children/adolescents with recurrent or refractory B7-H3–expressing primary CNS tumors or solid tumors metastatic to the CNS, including CNS-involved sarcoma and medulloblastoma/CNS metastatic settings where there is no curative standard option. The key angle is “compartmental” delivery—attempting to treat leptomeningeal/CNS disease while limiting systemic exposure compared with conventional external-beam approaches. Today’s care for these patients is individualized and often palliative: maximal safe surgery when feasible, prior radiation (often already used), and salvage systemic therapy or intrathecal approaches with limited durable control for CNS spread.