Toll-like receptors are a family of proteins that help generate immune responses against cancer and other pathogens. Entolimod, the lead drug candidate of Cleveland BioLabs Inc., of Buffalo, N.Y., activates toll-like receptor 5 (TLR5) and has been shown to have immunotherapeutic effects in preclinical cancer models.
Hatoon Bakhribah, MD, a Drug Development Fellow in Roswell Park’s Department of Medicine, will present results of this phase I clinical study at ASCO. Dr. Adjei and colleagues evaluated the agent’s safety, tolerability, pharmacokinetics, immunoactivity and preliminary antitumor activity in patients with a number of different advanced cancers, including colorectal, non-small-cell lung, anal and urothelial bladder tumors.
Among 26 participants in this dose-escalation study, eight patients had stable disease for more than six weeks following treatment with entolimod, and three patients maintained disease stability for longer than 12 weeks. The tolerability profile in patients with advanced cancer was similar to that observed in two previous studies in 150 healthy volunteers who received entolimod in a similar dose range. Mild-to-severe but manageable side effects such as hypotension and hyperglycemia, all of them anticipated effects of TLR5 activation, were observed in several patients. The results corroborated preclinical findings and suggest that entolimod should be further studied as an immunotherapeutic anticancer agent.
“Our findings are encouraging, as they suggest that entolimod can be safely combined with other chemotherapeutic, targeted or immunotherapeutic agents as treatment for advanced and very hard-to-treat cancers,” notes Dr. Adjei, who is Senior Vice President of Clinical Research and the Katherine Anne Gioia Chair in Cancer Medicine at Roswell Park. “We’ve identified a recommended dosing schedule for future studies.”
The study, “A phase I study of the toll-like receptor 5 (TLR5) agonist, entolimod, in patients with advanced cancers,” is abstract 3063 and will be presented on board no. 389 during the Developmental Therapeutics — Immunotherapy poster session on Saturday, May 30.