NCT03389802

Phase I Study of APX005M in Pediatric Central Nervous System Tumors

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
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 32 (actual)
• Sponsor: Pediatric Brain Tumor Consortium · Network
• Sex: All
• Age: 1 Year – 21 Years
• Healthy volunteers: Not accepted

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 stimulate cytokine release from lymphocytes and monocytes. APX005M can mediate a direct cytotoxic effect on CD40+ tumor cells.

Detailed 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.

Conditions

• Glioblastoma Multiforme
• High-grade Astrocytoma Not Otherwise Specified (NOS)
• CNS Primary Tumor, Not Otherwise Specified (NOS)
• Ependymoma, Not Otherwise Specified (NOS)
• Diffuse Intrinsic Pontine Gliomas (DIPG)
• Medulloblastoma

Interventions

Type	Name	Description
BIOLOGICAL	APX005M treatment for recurrent or refractory primary malignant CNS tumor patients	APX005M dosing will begin at 0.1 mg/kg, the APX005M dose may be increased (0.3, 0.45, 0.6 mg/kg) or decreased (0.03 mg/kg) in subsequent cohorts until the maximum tolerated dose (MTD) is reached or until dose level 3 (0.6 mg/kg) is complete without the MTD being defined. APX005M will be administered at the assigned dose level every 21 days (3 weeks). Patients may continue to receive APX005M for 36 courses (approximately 2 years) or until disease progression, unacceptable toxicity or death, whichever occurs first.
BIOLOGICAL	APX005M treatment for newly diagnosed DIPG patients	The starting dose of APX005M for the DIPG patients will be one dose level below the recommended phase II dose (RP2D) determined in Stratum 1 patients. The dose may be decreased or increased to the RP2D established in Stratum 1. APX005M will be administered at the assigned dose level every 21 days (3 weeks). Patients may continue to receive APX005M for 36 courses (approximately 2 years) or until disease progression, unacceptable toxicity or death, whichever occurs first.

Timeline

• Start date: 2018-03-01
• Primary completion: 2023-09-30
• Completion: 2026-06-30
• First posted: 2018-01-04
• Last updated: 2026-02-20
• Results posted: 2024-10-10

Locations

11 sites across 1 country: United States

Regulatory

• FDA-regulated drug study