Preclinical Results: Canine Phase I Safety Study of CM-101, a Tumor Capillary Specific Streptococcal Polysaccharide Toxin, for application in Spontaneous Canine Cancer

Abstract

Background: The study purpose was to evaluate canine safety of CM101, a polysaccharide Group B Streptococcus agalactiae tumor hemorrhagic toxin therapeutic. Hypothesis: CM101 specifically targets tumor vasculature as published in a human Phase 1 safety study that showed a wide therapeutic window. The hypothesis is that dogs should display a similar safety profile with low side-effects for CM101 canine cancer therapeutics. Animals: Considering the previous human safety trial, and in the interest of conserving purpose-bred dogs, on advice of USDA staff, we only used two healthy males, ~20 months old. Methods: USDA advice was to administer 10x the unit dose of 7.5ug/kg to 2 dogs and if no side effects, proceed to a pilot phase II. Given the dose was 10X the effective unit dose and twice the MTD in humans with stage 4 cancer, further dose escalation was not considered necessary. Dogs were given 10 units (75 ug/kg) CM101 in normal saline over 22 minutes intravenously. Blood and Urine were collected before infusion, intervals post infusion, and 2 weeks after. Under anesthesia through recovery, rectal temperature, heart rate and indwelling arterial blood pressure vital signs were monitored electronically. Clinical observations recorded through two weeks after infusion. Results: Total WBC (white blood cell) counts dropped below normal range two hours post-infusion, after 6-11 hours rising above the normal range, returning to baseline at 52 hours post-infusion. Creatinine kinase was elevated two hours post infusion returning to baseline in 6-72 hours. Urinalysis remained within normal limits. Conclusions and clinical importance: No adverse effects were observed when healthy dogs were given 10 units CM101. These finding suggest a wide therapeutic window for investigation in canine cancer.