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. CDX-1140 has shown direct anti-tumor activity in preclinical models of lymphoma.

Preclinical data, including the IND-enabling toxicology study of CDX-1140, were presented at the SITC Annual Meeting in November 2017. This toxicology study of CDX-1140 clearly demonstrates strong immune activation effects and low systemic toxicity. The data support the design of the Phase 1 study of CDX-1140 to rapidly identify the dose for characterizing single-agent and combination activity.

Ongoing Clinical Trials

Celldex has initiated an open-label, Phase 1 study, which is expected to enroll up to approximately 150 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. Secondary objectives of the study include analyses of safety and tolerability, pharmacodynamics, pharmacokinetics, immunogenicity and assessment of anti-tumor activity across a broad range of endpoints, such as objective response rate, clinical benefit rate, duration of response, progression-free survival and overall survival. Celldex believes that the potential for CDX-1140 will be best defined in combination studies with other immunotherapies or conventional cancer treatments. To this end, a combination therapy cohort of CDX-1140 with CDX-301 has also been initiated. CDX-301 is a dendritic cell growth factor that is being used as a priming agent to potentially increase the number of cells available to respond to CDX-1140. In addition, Celldex is evaluating the potential for combination with varlilumab, especially in lymphomas which co-express CD40 and CD27 receptors. Data from this ongoing Phase 1 study were presented at the Society for Immunotherapy of Cancer's (SITC) 33rd Annual Meeting 

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