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Cancer Biol Ther. 2010 Nov 15;10(10):983-93. doi: 10.4161/cbt.10.10.13251. Epub 2010 Nov 15.

Immune modulation with weekly dosing of an agonist CD40 antibody in a phase I study of patients with advanced solid tumors.

Author information

1
Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, USA.

Abstract

BACKGROUND:

Single-dose infusion of the agonistic anti-CD40 monoclonal antibody (mAb) CP-870,893 accomplishes immune activation and clinical responses in patients with advanced cancers, but repeat dosing of this agent has not been reported.

RESULTS:

Twenty-seven patients were enrolled. The most common adverse event was transient, infusion-related cytokine release syndrome (CRS). Dose-limiting toxicities included grade 3 CRS and grade 3 urticaria; the maximum tolerated dose (MTD) was estimated to be 0.2 mg/kg. Seven patients (26%) had stable disease as the best clinical response; no partial or complete responses were observed. At the MTD, patient B lymphocytes exhibited persistently increased expression of costimulatory and adhesion molecules without resetting to baseline between doses. In 4 of 8 patients (50%) evaluated at the MTD, there were marked declines in total CD3(+) T lymphocytes, as well as CD4(+) and CD8(+) subsets.

PATIENTS AND METHODS:

Patients with advanced solid tumor malignancies received weekly intravenous infusions of CP-870,893 in four dose level cohorts. Safety and immune pharmacodynamics were assessed.

CONCLUSIONS:

Weekly infusions of the agonist CD40 antibody CP-870,893 were well-tolerated, but there was little clinical activity in advanced cancer patients. Correlative studies demonstrate chronic B cell activation and in some patients, T cell depletion. Longer dosing intervals may be desirable for optimal immune pharmacodynamics.

PMID:
20855968
PMCID:
PMC3047092
DOI:
10.4161/cbt.10.10.13251
[Indexed for MEDLINE]
Free PMC Article

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