Celldex Therapeutics, Inc. (NASDAQ: CLDX) announced positive results from a Phase 1 multi-dose study of CDX-301 (FMS-like tyrosine kinase-3 ligand) demonstrating that CDX-301 was well-tolerated and can safely and effectively mobilize hematopoietic cell populations in healthy volunteers. The data support future development of CDX-301 in a number of indications, including hematopoietic stem cell transplant and cancer immunotherapy. Results were presented in a poster entitled “A Phase 1 Trial of the Hematopoietic Growth Factor CDX-301 (rhuFlt3L) in Healthy Volunteers” on Monday, December 10, 2012 at 6:00 pm ET at the American Society of Hematology 54th Annual Meeting and Exposition. The lead author was Niroshana Anandasabapathy, MD, PhD, Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY.
“The data presented today confirm previous studies and support continued development of CDX-301, both alone and in combination with other Celldex assets across a broad range of indications,” said Thomas Davis, MD, Senior Vice President and Chief Medical Officer. “In particular, we believe CDX-301 holds significant potential for use in hematopoietic stem cell transplant, where it has demonstrated improvement of blood cell reconstitution in preclinical in vivo models. Data from the Phase 1 study will enable us to define an appropriate dosing regimen for this indication and future indications. We intend to work with collaborators, including academic institutions and government agencies, to conduct future studies.”
30 healthy volunteers were enrolled across seven cohorts. The first five cohorts assessed escalating doses of CDX-301 (from 1 ug/kg to 75 ug/kg) as a five-day regimen, while the final two cohorts assessed CDX-301 (at 25 ug/kg) as seven- and 10-day regimens. All volunteers completed dosing and safety follow-up. Short-term dosing of five days resulted in significant mobilization of dendritic and stem cells, with the highest levels of mobilization achieved at the maximum dose. Ten-day dosing significantly enhanced the circulation of white blood cells and monocytes compared to the five-day regimen. Analysis on the expansion of stem cells, dendritic cells and other cell populations are still being conducted and will be presented at a future medical meeting. CDX-301 was generally well-tolerated. Transient Grade 1 lymphadenopathy was observed in five volunteers and Grade 1 diarrhea was observed in two volunteers. One possible dose-limiting toxicity (DLT) was observed in a volunteer with a remote history of community acquired pneumonia (CAP) who developed CAP on study day 12. The volunteer responded rapidly to antibiotics and fully recovered. No additional infections or DLTs were observed in the study. No anti-CDX-301 antibodies were detected in any volunteers through the end of study follow-up.