Celldex Announces Varlilumab Continues to Show Very Favorable Profile

Celldex Therapeutics, Inc. CLDX today reported data from its ongoing Phase 1 study of the fully human monoclonal antibody varlilumab (CDX-1127) in cancer. Varlilumab is an immunotherapy designed to enhance the body's natural immune response by directly activating T cells that can specifically recognize and kill cancer cells. Preclinical data support the broad study of varlilumab in combination with a number of other anti-cancer agents including but not limited to checkpoint inhibitors, chemotherapies, targeted therapies and vaccines. Varlilumab will enter at least four combination studies in the second half of 2014. Results presented included data from the lymphoid malignancies dose-escalation arm and solid tumor expansion cohorts in metastatic melanoma and renal cell carcinoma. Varlilumab was very well tolerated and demonstrated clear biologic activity and promising signs of clinical activity in advanced, treatment-refractory patient populations—all of which provide the rationale for combination studies with other immune activating therapies. Results were presented in two poster sessions (poster #16 and 19) at the American Society of Clinical Oncology (ASCO) Annual Meeting 2014 on Monday, June 2, 2014 from 1:15 to 4:15 p.m. CDT. In addition, the data will be discussed during a Poster Highlight Session entitled "Modulating the Anti-tumor Immune Response" by Dr. Cassian Yee of The University of Texas MD Anderson Cancer Center today at 5:15 CDT. "This first-in-man study for a CD27 agonist antibody documented significant immunological effects of varlilumab, most notably activation of T cells, including de novo responses to previously defined tumor antigens, and impressive decreases in regulatory cells—both of which have been shown to be necessary to generate optimal anti-cancer immune responses," said Tim Bullock, PhD, Associate Professor of Pathology, University of Virginia School of Medicine, who led the immune monitoring on the solid tumor arm of the Phase 1 varlilumab study. "Importantly, varlilumab was able to elicit these biological effects while also demonstrating a benign safety profile--suggesting that combination therapies involving varlilumab will not be limited by unacceptable toxicities. Moving forward, in these combination studies, it will be important to further elucidate how the dose and timing of varlilumab administration impact the biological and clinical effects so we can optimize clinical benefit for patients with cancer." "Varlilumab's minimal toxicity and ability to specifically activate the immune system while acutely reducing measurable regulatory T cells make it an ideal agent to use with checkpoint inhibition and other anti-tumor approaches," said Tom Davis, MD, Senior Vice President and Chief Medical Officer of Celldex Therapeutics. "We are focused on the initiation of an expanded combination program with internal programs and external collaborators, including several checkpoint inhibitors and other molecularly targeted agents. We believe varlilumab has significant potential and these studies will further add to our understanding of this program." Varlilumab targets CD27, a critical molecule in the activation pathway of lymphocytes. CD27 can be effectively manipulated with activating antibodies to induce potent anti-tumor responses and may result in fewer toxicities due to its restricted expression and regulation. Varlilumab is a potent anti-CD27 agonist that induces activation and proliferation of human T cells when combined with T cell receptor stimulation. In lymphoid malignancies that express CD27 at high levels, varlilumab may have an additional mechanism of action through a direct anti-tumor effect.