Phase 1, Open-Label, Dose-Escalation Study of CP-870,893 in Patients With Solid Tumors

CD40, a member of the Tumor Necrosis Factor receptor superfamily, is expressed on many tumor types, including melanoma, prostate, colon, breast, renal, pancreatic, and nonsmall cell lung cancers. In preclinical models, activation of CD40 results in increased antigen presentation and induction of apoptosis. CD40 is also expressed on antigen presenting cells (APCs) (B cells, dendritic cells, monocytes) and is a key regulator of both cellular and humoral immune responses. Activation of CD40 by CP-870,893, an agonistic anti-CD40 monoclonal antibody, enhances host immune responses and abrogates the growth of tumors independently of the expression of CD40 on tumor cells. Therefore, it is hypothesized that therapeutic intervention with CP-870,893 may be beneficial to a large number of cancer patients either through an immunomodulatory effect or through a direct effect on CD40-positive tumor cells.