Date: 2016-06-04
Type of information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago
Company: Celldex Therapeutics (USA - NJ) National Cancer Institute (USA)
Product: CDX-1401 and CDX-301
Action
mechanism: cytokine/fusion protein/monoclonal antibody/immunotherapy product. CDX-301 (Flt3L) is a potent hematopoietic cytokine that has demonstrated a unique capacity to increase the number of circulating dendritic cells in both laboratory and clinical studies. In addition, CDX-301 has shown impressive results in models of cancer, infectious diseases and inflammatory/autoimmune diseases. Celldex believes this ligand may hold significant opportunity for synergistic development in combination with other proprietary molecules in the Company's portfolio.
CDX-1401 is an NY-ESO-1-antibody fusion protein for immunotherapy, which is designed to activate the patient's immune system against cancers that express the tumor marker, NY-ESO-1. CDX-1401 consists of a fully human monoclonal antibody with specificity for the dendritic cell receptor DEC-205 genetically linked to the NY-ESO-1 tumor antigen. Celldex has accessed NY-ESO-1 through a licensing agreement with the Ludwig Institute for Cancer Research. By selectively delivering the NY-ESO-1 antigen to dendritic cells in the body, CDX-1401 is intended to induce robust immune responses against the antigen-expressing cancer cells.
Disease: malignant melanoma
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: This randomized phase II trial studies how well DEC-205/NY-ESO-1 fusion protein CDX-1401 (CDX-1401) and neoantigen-based melanoma-poly-ICLC vaccine (poly-ICLC) vaccine therapy work when given with or without recombinant flt3 ligand (CDX-301) in treating patients with stage IIB-IV melanoma. The cancer vaccine CDX-1401 attaches to a protein that is made in tumor cells. The vaccine helps the body recognize the tumor to fight the cancer. The CDX-301 vaccine may help the body make more of the tumor fighting cells, known as dendritic cells. The poly-ICLC vaccine stimulates the immune system and may help these dendritic cells mature so that they can recognize the tumor. It is not yet known whether CDX-1401 and poly-ICLC will work better with or without CDX-301 in treating melanoma. (NCT02129075)
Latest
news: * On June 4, 2016, Celldex Therapeutics announced results from a Phase 2 clinical study evaluating CDX-1401 and CDX-301 in patients with malignant melanoma, which was conducted by the Cancer Immunotherapy Trials Network (CITN) under a Cooperative Research and Development Agreement (CRADA) between Celldex and the Cancer Therapy Evaluation Program of the National Cancer Institute. CDX-1401 is an NY-ESO-1-antibody fusion protein for immunotherapy, and CDX-301 (recombinant human Flt3 ligand) is a potent hematopoietic cytokine that uniquely expands dendritic cells and hematopoietic stem cells. Results from the study were presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago in a poster titled "A Phase 2, Open-label, Multicenter, Randomized Study of CDX?1401, a Dendritic Cell Targeting NY-ESO-1 Vaccine, in Patients with Malignant Melanoma Pre-Treated with CDX-301, a Recombinant Human Flt3 Ligand." The study randomized 60 patients with resected stage IIb through IV melanoma into two cohorts (n=30 each) to assess whether the immune response to NY-ESO-1 elicited by CDX-1401 could be substantially increased by pre-treatment with CDX-301 to expand the number of dendritic cells, which are key cells in initiating immune responses. As this study was intended primarily for safety and immune endpoints, patients were not selected for NY?ESO?1 expression. Both treatment cohorts received four monthly cycles of CDX-1401 and poly-ICLC (Hiltonol®). Cohort 1 received pre-treatment with CDX-301 for the first two cycles, whereas Cohort 2 did not receive CDX-301 . Both combination regimens were well tolerated, and no drug-related adverse events required discontinuation from treatment. NY-ESO-1 specific T cell responses were significantly greater and developed earlier in Cohort 1 compared to Cohort 2. In addition, all patients in Cohort 1 (n=30) achieved a specific NY-ESO-1-specific T cell response compared to 22 out of 30 patients in Cohort 2. Substantial increases in innate immune cells (dendritic cells, natural killer cells and monocytes) and greater increases in antibody titer were observed in the CDX-301 pre-treated Cohort 1. "This study confirms that CDX-1401 is effective at driving NY-ESO-1 immunity and further shows the value of CDX-301 as a combination agent for enhancing tumor-specific immune responses," said Thomas Davis, M.D., Executive Vice President and Chief Medical Officer of Celldex Therapeutics. "With these results, we are initiating a targeted study in patients with NY-ESO-1 positive disease to determine if these enhanced immune responses can translate to improved clinical outcomes."
