Principal Institutions: Memorial Sloan Kettering Cancer Center and Pediatric Brain Tumor Consortium (PBTC) – This early phase, multicenter, open-label study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, and preliminary efficacy of APX005M in children and young adults with malignant brain tumors.

APX-005M is a humanized antibody that binds to CD40. Signaling through CD40 on antigen presenting cells (APCs) in the immune system enhances the T-cell response due to improved antigen presentation and cytokine release. Therefore, a CD40-agonistic antibody can activate and stimulate both innate and adaptive immunity. These mechanisms do not require CD40 expression on the tumor cells. APX005M is capable of stimulating antigen-specific T-cell responses to alloantigens, viral antigens, and tumor antigens. CD40 is also expressed on many tumor cells and can mediate an antibody-directed cytotoxic effect. APX005M is generally well tolerated and is currently being developed for the treatment of malignant solid tumors in adults. This phase I clinical trial will test APX005M in children with recurrent or refractory primary malignant CNS tumor or newly diagnosed DIPG and will be administered by intravenous infusion over 60 minutes once every 3 weeks for 36 courses (2 years). This study will enroll up to 24 children and determine the recommended phase II dose, describe toxicities, and assess responses.

Exploratory objectives are to (1) assess the incidence of anti-drug antibodies, (2) determine the immune pharmacodynamics of APX005M and (3) identify tumor and blood efficacy and/or resistance biomarkers.