Phase I Study of APX005M in Pediatric CNS Tumors

Glioblastoma Multiforme Clinical Trial

Official title: Phase I Study to Evaluate the Safety and Tolerability of the CD40 Agonistic Monoclonal Antibody APX005M in Pediatric Subjects With Recurrent/Refractory Brain Tumors and Newly Diagnosed Brain Stem Glioma

Status Active, not recruiting

Clinical Trial Summary

This phase I trial studies the side effects and best dose of APX005M in treating younger patients with primary malignant central nervous system tumor that is growing, spreading, or getting worse (progressive), or newly diagnosed diffuse intrinsic pontine glioma. APX005M can trigger activation of B cells, monocytes, and dendritic cells and stimulat cytokine release from lymphocytes and monocytes. APX005M can mediate a direct cytotoxic effect on CD40+ tumor cells.

Clinical Trial Description

This is a multicenter phase I trial of APX005M in patients with recurrent or refractory primary malignant central nervous system tumor, or newly diagnosed diffuse intrinsic pontine glioma. APX005M is a humanized IgG1κ mAb that binds to CD40. APX005M binds to both human and cynomolgus monkey CD40 with high affinity, triggering activation of B cells, monocytes, and dendritic cells and stimulating cytokine release from both human and monkey lymphocytes and monocytes. APX005M does not bind to mouse or rat CD40. CD40 is also expressed on many human tumor cells, and APX005M can mediate a direct cytotoxic effect on CD40+ tumor cells. Activation of CD40 on tumor cells results in tumor cell apoptosis and inhibition of tumor growth. CD40 agonistic antibodies have demonstrated potent antitumor immune response stimulation in both animal models and cancer patients. Due to its action on both immune and tumor cells, CD40 has been studied as a target for novel cancer immunotherapy. Apexigen has declared the adult recommended phase 2 dose to be 0.3 mg/kg because no dose limiting toxicities were encountered at that dose and the pharmacodynamic profile was similar to the 1 mg/kg maximally tolerated dose. This phase 1 clinical trial is to study APX005M in children with central nervous system tumors. ;

Related Conditions & MeSH terms

• Astrocytoma
• CNS Primary Tumor, Nos
• Diffuse Intrinsic Pontine Glioma
• Diffuse Intrinsic Pontine Gliomas (DIPG)
• Ependymoma
• Ependymoma, NOS
• Glioblastoma
• Glioblastoma Multiforme
• Glioma
• High-grade Astrocytoma NOS
• Medulloblastoma

• NCT number: NCT03389802
• Study type: Interventional
• Source: Pediatric Brain Tumor Consortium
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 1, 2018
• Completion date: September 30, 2024