Celldex’s primary focus is in oncology. There are four programs currently in clinical development for treatment of multiple cancers and additional programs are progressing toward clinical development.
Rindopepimut (CDX-110) - Vaccine for EGFRvIII-expressing tumors:
Our lead clinical development program, rindopepimut, is an immunotherapy that targets the tumor specific oncogene called EGFRvIII, a functional and permanently activated mutation of the epidermal growth factor receptor (EGFR), a protein that has been well validated as a target for cancer therapy. Unlike EGFR, EGFRvIII has not been detected at a significant level in normal tissues, but has been identified in multiple cancer types; therefore, targeting of this tumor-specific molecule is not likely to impact healthy tissues, EGFRvIII can turn normal cells into malignant cells through its well documented oncogenic properties, providing a constant growth signal to tumor cells which express it. Consequently, cells producing EGFRvIII have an enhanced capacity for unregulated growth. Rindopepimut is designed to activate the patient’s own immune system against tumor cells expressing the EGFRvIII mutation. For citations related to rindopepimut, including the recently reported results on the Phase 2 multicenter clinical trial (ACT III), click here. For information about enrolling in Clinical Trials with rindopepimut, including the Phase 3 trial in EGFRvIII-expressing primary glioblastoma, click here.
- CDX-011 - Antibody-Drug Conjugate for the Treatment of Metastatic Breast Cancer and Advanced Melanoma:
CDX-011 is a fully-human monoclonal antibody-drug conjugate (ADC) that targets glycoprotein NMB (GPNMB). GPNMB is a protein overexpressed by multiple tumor types, including melanoma, breast cancer and glioma. GPNMB has been shown to be associated with the ability of the cancer cell to invade and metastasize, and to correlate with reduced time to progression and survival in breast cancer. The GPNMB-targeting antibody, CR011, is linked to a potent cytotoxic, monomethyl auristatin E (MMAE), using Seattle Genetics’ proprietary technology. CDX-011 is designed to be stable in the bloodstream, but to release MMAE upon internalization into GPNMB-expressing tumor cells, resulting in a targeted cell-killing effect. For citations related to CDX-011, including the positive results of Phase 1/2 clinical trials in advanced breast cancer and melanoma, click here. For information about current Clinical Trials with CDX-011, click here.
- CDX-1401 - Treatment of Multiple Tumors:
CDX-1401 is a fusion protein consisting of a fully human monoclonal antibody with specificity for the dendritic cell receptor, DEC-205, linked to the NY-ESO-1 tumor antigen. This product uses our APC Targeting Technology™ and is intended to selectively deliver the NY-ESO-1 antigen to Antigen-Presenting Cells (APCs) for generating robust immune responses against cancer cells expressing NY-ESO-1. NY-ESO-1 represents an important target for developing therapeutics against multiple cancers. The antigen, which is expressed in a wide variety of cancer cells but not at significant levels in most normal tissues, has been extensively characterized in pre-clinical and clinical studies and has been found to be highly immunogenic. For information about Clinical Trials with CDX-1401, click here. For citations related to CDX-1401 click here.
- CDX-1127 - Cancer Immunotherapy:
CDX-1127 is an agonist anti-CD27 monoclonal antibody (mAb) that is expected to activate CD27 expressing T cells in the context of T cell receptor stimulation. In addition to the immune enhancing properties of CDX-1127, the mAb may also provide direct therapeutic effects against tumors with CD27 expression. In pre-clinical models, antibodies to CD27 alone have been shown to mediate anti-tumor effects and may be particularly effective in combination with other immunotherapies. CD27 is a critical molecule in the activation pathway of lymphocytes. It is downstream from CD40 and may provide a novel way to regulate the immune responses. Engaging CD27 with the appropriate monoclonal antibody has proven highly effective at promoting anti-cancer immunity in mouse models. For information about Clinical Trials with CDX-1127, click here. For citations related to CDX-1127 click here.
- CDX-301 - Clinical Program for Treatment of Cancer Patients Requiring Hematopoietic Stem Cell Transplantation (HSCT)
CDX-301 is soluble, recombinant human FMS-like tyrosine kinase-3 ligand (Flt3L) that acts by uniquely binding FMS-like tyrosine kinase-3 (Flt3, CD135) which is expressed on hematopoietic stem cells (HSC), early progenitor cells, immature thymocytes, and steady state dendritic cells, resulting in the proliferation, differentiation, development and mobilization of these cells in the bone marrow, peripheral blood, and lymphoid organs. Prior development of this program was performed by Immunex, Inc. demonstrating the safety and biologic activity in early clinical studies. A Phase 1 trial in healthy volunteers is underway to support subsequent trials for allogeneic HSCT. Celldex will eventually pursue additional indications potentially to include cancer therapy, ex vivo expansion of dendritic cells for cancer immunotherapy, radiation countermeasures, and burn management. For information about Clinical Trials with CDX-301, click here. For citations related to CDX-301 click here.
- CDX-014 - Treatment of Multiple Tumors:
CDX-014 is a fully-human monoclonal ADC that targets TIM-1, an immunomudulatory protein that appears to down regulate immune response to tumors. The antibody, CR014, is linked to a potent chemotherapeutic, monomethyl auristatin E (MMAE), using Seattle Genetics’ proprietary technology. The ADC is designed to be stable in the bloodstream, but to release MMAE upon internalization into TIM-1-expressing tumor cells, resulting in a targeted cell-killing effect. CDX-014 has shown potent activity in preclinical models of ovarian and renal cancer. For citations related to CDX-014
- CDX-1307 - Cancer Program Using APC Technology:
CDX-1307 is a fusion protein composed of a human 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. hCG-β is an established tumor-associated antigen that is over-expressed in a variety of common cancers including those of the colon, lung, pancreas, esophagus, breast, bladder, cervix, stomach, and prostate, but not expressed in most normal tissues. Elevated hCG-β serum levels and/or tissue expression have been shown to be an independent predictor of poor disease outcome and associated with a more aggressive disease course. Mechanistically, it has been proposed that hCG-β may function at several different levels to facilitate cancer progression: as a transforming growth factor, an immunosuppressive agent, an inducer of metastasis, and/or as an angiogenic factor. CDX-1307 has been evaluated for the treatment of advanced colorectal, pancreatic, bladder, ovarian and breast cancers in two Phase 1 trials. For citations related to CDX-1307, including results of Phase 1 clinical trials, click here. To submit an inquiry or proposal for collaborative development, click here.