A Phase 0/1 Clinical Trial With an Expansion Phase of GSK5764227, a B7-H3-Targeted Antibody-Drug Conjugate (ADC), in Patients With Recurrent Grade 4 Glioma and Patients With Brain Metastases

Must have received: standard of care therapy

progressed on or following standard of care therapy, including maximal safe resection (biopsy allowed if resection was deemed unsafe) and concurrent chemoradiation

Cannot have received: B7-H3 targeted agent (orlotamab, enoblituzumab, I-Dxd)

Orlotamab, enoblituzumab, I-Dxd, or other B7-H3 targeted agents

Cannot have received: investigational agent

Investigational agent within 4 weeks prior to the first infusion of study drug

Cannot have received: cytotoxic chemotherapy

Cytotoxic chemotherapy or anticancer drugs within 14 days prior to the first infusion of study drug

Cannot have received: monoclonal antibody

Monoclonal antibody within 28 days prior to the first infusion of study drug

Cannot have received: immunosuppressive agent

Exception: A stable or reduced daily dose of 8 mg dexamethasone for management of GBM-related edema and its associated symptoms within 14 days prior to dosing is permitted; low dose corticosteroids (prednisone ≤10 mg/day or equivalent) may be administered and use of inhaled or topical steroids and prophylactic corticosteroids for procedures are permitted.

Immunosuppressive agents within 30 days prior to the first infusion of study drug, or requires long-term (30 days or longer) glucocorticoid therapy

Cannot have received: strong/moderate CYP3A4, CYP2D6, P-gp, or BCRP inhibitor

Strong/moderate inhibitors of CYP3A4, CYP2D6, P-gp, or BCRP, within 7 days prior to the first infusion of study drug; or need to continue treatment with these drugs

Cannot have received: colony-stimulating factor (G-CSF, granulocyte-macrophage colony-stimulating factor, recombinant erythropoietin)

administration of colony-stimulating factors (including G-CSF, granulocyte-macrophage colony-stimulating factor, or recombinant erythropoietin) with 14 days prior to enrollment