CD40 Agonist Active Against Solid Tumors

[RhondaH]

CD40 Agonist Active Against Solid Tumors





By David Douglas

NEW YORK (Reuters Health) Mar 21 - CP-870,893, a novel CD40 agonist monoclonal antibody, showed antitumor activity in a phase I dose-escalation study, researchers report in the March 1st issue of the Journal of Clinical Oncology.

"This new antibody," lead investigator Dr. Robert H. Vonderheide told Reuters Health, "is designed to kill tumor cells directly while simultaneously enhancing patients' immune responses against cancer."

Dr. Vonderheide of the Abramson Cancer Center of the University of Pennsylvania, Philadelphia and colleagues note that the cell-surface molecule CD40 activates antigen-presenting cells (APCs) and enhances immune responses. It is also expressed in many tumor cells and mediates a direct cytotoxic effect.

CP-870,893 is a fully humanized and selective CD40 agonist monoclonal antibody that has both direct and indirect effects on tumor cell death. It has been shown to activate human APCs in vitro and inhibit growth of human tumors in mice.

To further test for safety and biologic impact, the researchers gave 29 patients with advanced solid tumors CP-870,893 in doses from 0.01 to 0.3 mg/kg.

Dose-limiting toxicity was seen in 2 of 7 patients given 0.3 mg/kg. The most common adverse event was cytokine release syndrome seen in 55% of patients. This was transient and most pronounced in patients at the 0.2 and 0.3 mg/kg level. The syndrome involves symptoms including chills, fever and nausea.

On restaging at day 43 -- at the end of the study -- 4 patients with melanoma had objective partial responses. This group comprised 27% of melanoma patients and 14% of all patients.

Seven patients with stable disease or partial remission were re-dosed and one, who has had eight doses, remains in partial remission at 14 months. Retreatment was not associated with additional toxicities.

"If subsequent clinical trials confirm safety and effectiveness in patients, I hope this CD40 antibody could one day be useful for treating many different types of patients with cancer," concluded Dr. Vonderheide.

J Clin Oncol 2007;25:876-883.