CDX-1140 is a fully human antibody targeted to CD40, a key activator of immune response which is found on dendritic cells, macrophages and B cells and is also expressed on many cancer cells. Potent CD40 agonist antibodies have shown encouraging results in early clinical studies; however, systemic toxicity associated with broad CD40 activation has limited their dosing. CDX-1140 has unique properties relative to other CD40 agonist antibodies: potent agonist activity is independent of Fc receptor interaction, contributing to more consistent, controlled immune activation; CD40L binding is not blocked, leading to potential synergistic effects of agonist activity near activated T cells in lymph nodes and tumors; and the antibody does not promote cytokine production in whole blood assays. 

Ongoing Clinical Trials

Celldex has initiated an open-label, Phase 1 study in patients with recurrent, locally advanced or metastatic cancers. It is designed to determine the maximum tolerated dose during a dose-escalation phase and to recommend dose(s) for further study in a subsequent expansion phase. The expansion phase is designed to further evaluate the tolerability and biologic effects of selected dose(s) of CDX-1140 in specific tumor types. The study includes both monotherapy and combination cohorts with CDX-301, Celldex’s dendritic cell growth factor, designed to increase the number of dendritic cells which are critical to initiating antitumor immunity and are a key target for CDX-1140. Celldex intends to add additional combination cohorts with mechanisms that the Company believes could be complementary or synergistic. Interim data from this ongoing Phase 1 study were presented at the Society for Immunotherapy of Cancer's (SITC) 34rd Annual Meeting.

Both the monotherapy and combination with CDX-301 dose escalation portions of the trial are complete with an identified maximum tolerated dose (MTD) and recommended Phase 2 dose of CDX-1140 at 1.5 mg/kg—one of the highest systemic dose levels in the CD40 agonist class. Expansion cohorts are actively recruiting including:

--   CDX-1140 with KEYTRUDA® (pembrolizumab) in patients who have progressed on checkpoint therapy; and,
--   CDX-1140 with standard of care chemotherapy in patients with 1st line metastatic pancreatic cancer.

For more information on the CDX-1140 program, view recent scientific presentations and publications.