CDX-1307: Clinical Program

A vaccine for hCG-β expressing malignancies

Our first APC Targeting Technology™ product candidate, CDX-1307, is in development for the treatment of metastatic or locally advanced breast, colorectal, pancreatic, ovarian or bladder cancers that express the beta chain of human chorionic gonadotropin (hCG-β). hCG-β is an established tumor-associated antigen often found in tumors of these types of cancer, but not in most normal tissues. Elevated hCG-β serum levels and/or tissue expansion have been shown to be an independent predictor of disease outcome and are associated with a more aggressive disease course. CDX-1307 is a fusion protein composed of a mannose receptor (MR)-specific human monoclonal antibody and the hCG-β antigen. This antibody-vaccine is designed to deliver the antigen hCG-β to dendritic cells (DCs) and induce hCG-β specific cellular and humoral immune responses, thus activating the patient’s immune system against cancers that express hCG-β.

CDX-1307: Phase 1 Program

Celldex has conducted two Phase 1 studies that explore different routes of administration of CDX-1307.

• Trial CDX-1307-01: A Phase 1 study of CDX-1307 given into the skin (intradermally)
• Trial CDX-1307-02: A Phase 1 study of CDX-1307 given into the blood (intravenously)

About the Clinical Trials

These trials, which include more than 80 patients, evaluate the safety immune response and biologic activity of CDX-1307 vaccine given alone or with immune stimulators in patients with metastatic or unresectable locally advanced breast, colorectal, pancreatic, ovarian or bladder cancers. Patients are dosed every two weeks for a total of four doses. Initial dose evaluation of CDX-1307 has been followed by evaluation of the vaccine given with immunomodulatory agents (agents that can increase the strength of an immune response). These agents include GM-CSF (a growth factor and stimulator of immune cells), poly-ICLC (Hiltonol™, provided by Oncovir, Inc., a TLR3 agonist and stimulator of immune cells) and Resiquimod (a TLR7/8 agonist and stimulator of immune cells provided by 3M).

As presented at the 24th Annual Meeting of the International Society for Biological Therapy of Cancer, the data from these Phase 1 studies have demonstrated enhanced immunological and biological responses in the enrolled patients, who were heavily pre-treated (average of 4.6 prior therapies) and had advanced-stage cancers. All patient cohorts demonstrated a favorable safety profile with no dose limiting toxicity to date. The combination of CDX-1307 with TLR agonists significantly enhanced immune responses against hCG-β, providing strong humoral responses in 88% of patients and cellular immune responses in 57% of patients analyzed to date. Immune responses occurred even in the presence of high circulating levels of hCG-β, suggesting that CDX-1307 can overcome antigen tolerance in advanced and heavily pretreated cancers. Nine patients with breast, colorectal, pancreatic and testicular cancers experienced disease stabilization from 2.3 months to 11.4 months following the initiation of CDX-1307 vaccination. Two of these patients have received multiple courses of CDX-1307 and continue treatment with stable disease at 6.4 and 11.4 months. In order to determine if higher dose impacts immune and clinical responses, an additional cohort combining dual TLR agonists and an increased CDX-1307 dose (15 mg) has also been enrolled (data are pending).

CDX-1307: Phase 2 Program

The Phase 1 data provide the basis for advancing CDX-1307 into a front-line patient population selected for hCG-β expressing cancers. Celldex is planning the initiation of a Phase 2 study in patients with newly diagnosed bladder cancer in the first quarter of 2010.