Cleveland BioLabs Releases Entolimod Phase 1 Study Findings at ASCO

Cleveland BioLabs, Inc.

today announced the release of results from a Phase 1 open-label, dose-escalation trial of entolimod in patients with advanced cancer at the 2015 annual meeting of the American Society of Clinical Oncology (ASCO), held from May 29 - June 2 in Chicago, Illinois. Entolimod is a specific, toll-like receptor 5 (TLR5) agonist that has shown preclinical potential in the immunotherapy of cancer. Entolimod administration activates innate and adaptive immune responses and mobilizes immunocytes to organs that have high TLR5 expression. These organs include liver and lung (common sites of metastases for many tumors) as well as bladder uroepithelium, which undergoes malignant transformation during the development of bladder cancers. The study was undertaken to evaluate entolimod's safety, tolerability, pharmacokinetics, immunoactivity and preliminary antitumor activity. Twenty-six patients ranging in age from 46 to 82 years were enrolled in the study. All had previously treated metastatic cancers, including colorectal, non-small cell lung, anal and urothelial bladder tumors. The study evaluated an 8-fold range of subcutaneous dose levels from 5 to 40 µg/dose administered as 4 or 5 injections within a 2-week period. Pharmacokinetic and pharmacodynamic measurements and immune function samples were obtained pre- and post-dosing. Stable disease for more than 6 weeks was observed in 8 patients with various cancer types; among these, 3 patients (with anal, colorectal and urothelial cancers) had maintenance of stable disease for more than 12 weeks. Patients exhibited CD8+ T-cell activation with stable or decreased levels of myeloid-derived suppressive cells, accompanied by increased immunostimulatory cytokines (G-CSF, IL-6, and IL-8). The tolerability profile in patients with advanced cancer was similar to that observed in two previously conducted studies in 150 healthy volunteers receiving entolimod. As expected with activation of innate immune pathways, common adverse events were flu-like symptoms and fever, with some patients having transient, spontaneously resolving tachycardia, hypotension, and hyperglycemia. Overall, treatment with entolimod was well tolerated. Alex Adjei, M.D., Ph.D., F.A.C.P., Chairman of the Department of Medicine and Senior Vice President of Clinical Research at Roswell Park Cancer Institute, and principal investigator for the trial, stated: "Entolimod offers a novel immunotherapeutic approach to cancer that is distinct from other methods currently in development. Drug-related side effects consistent with intended TLR agonism were transient and manageable, even in this very ill population with multiple comorbidities. The safety and immunological data suggest that entolimod can be combined with chemotherapeutic, targeted, or other immunotherapeutic anticancer agents or vaccines." Langdon Miller, M.D., President and Chief Medical Officer of CBLI, noted: "Observations made during this trial corroborate preclinical findings and strongly support the hypothesis that entolimod has potential as an immunotherapeutic agent. We are performing a follow-on study in Moscow, Russia, to extend the clinical observations from the higher entolimod dose levels evaluated in this trial. Additionally, given the safety and immunological data acquired in this completed entolimod study, we are evaluating combinations with immune checkpoint inhibitors in preclinical models of breast, colon and bladder cancer and continuing to explore the potential for entolimod as a local (intravesical) therapy for non-invasive bladder cancer." The poster, "A Phase I Study of the Toll-Like Receptor 5 (TLR5) Agonist, Entolimod in Patients (Pts) With Advanced Cancers," is abstract no. 3063 and was presented on board no. 389 by Hatoon Bakhribah, MD, a Drug Development Fellow at Roswell Park Cancer Institute during the Developmental Therapeutics-Immunotherapy poster session on Saturday May 30, 2015.