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 with CDX-1140 and has prioritized a combination with KEYTRUDA® (pembrolizumab). Interim data from this ongoing Phase 1 study were presented at the Society for Immunotherapy of Cancer's (SITC) 34rd Annual Meeting. The monotherapy arm has been completed with an identified maximum tolerated dose (MTD) and recommended Phase 2 dose of 1.5 mg/kg, one of the highest systemic dose levels achieved in the CD40 agonist class. The combination cohort with CDX-301 has been generally well tolerated to date and the cohort is progressing on track. Based on promising clinical activity observed in patients with head and neck squamous cell carcinoma in the monotherapy arm of the study, an expansion cohort of 15 patients has been added to further explore this potential. 

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