Dr. Maria Reig, head of the Barcelona Clinic Liver Cancer (BCLC) Unit at Hospital Clinic Barcelona has developed an experimental drug that inhibits an enzyme playing a crucial role in cell division and growth. The drug, NMS-01940153E, has shown signs of anti-cancer activity with manageable side effects in liver cancer patients, she reported in an abstract at the 34th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics held recently in Barcelona, Spain.
NMS-01940153E was designed as a selective inhibitor of monopolar spindle 1 (MPS1), a kinase that is overexpressed in several cancers including liver cancer. MPS1 plays a critical role in regulating the processes involved in cell division and growth and leads to cancer if it ceases to function properly.
“Primary liver cancer is the sixth most common cancer and among the leading causes of cancer-related deaths worldwide. Although new treatments options are becoming available, the overall prognosis for advanced liver cancer remains poor,” noted Reig. “I wanted to find new treatments for this cancer.”
In the small trial testing the drug, 12 patients who had already been given three treatments for their cancer that had failed, were given NMS-01940153E on days one, eight and 15 in a recurring four-week cycle at increasing doses starting at 100mg per meter of body surface area per week.
Out of 11 patients who could be evaluated to see if the drug was making an impact, the tumor shrank by at least 30% in two of them for 2.5 and 9.3 months. Both discontinued treatment after their cancer started to grow again at 6.5 and 11.1 months, respectively. Another two patients had long-lasting stable disease and are still receiving the treatment after 11 and 18 cycles.
“At the 100 mg/m2/w dose, one of six patients who could be evaluated, had a partial response to the study drug. At the 135 mg/m2/w dose, one of five had a partial response,” Reig said. “Since each patient had three prior failures with standard treatments, the responses to NMS-01940153E are a strong sign that this new mechanism might be valuable in liver cancer, especially for patients whose cancer has already failed to respond to standard options.”
To measure potential toxicity of the drug, the clinicians increased dosing. At doses of 135mg/m2/week, two of the patients experienced reduced white blood cell counts with sepsis or urinary tract infection that were serious enough to halt dosing increases. Other side effects included Other side effects included abnormally-coloured urine, low platelet counts, anemia, weakness, diarrhea, and reaction at the site of the injection.
NMS-01940153E entered a Phase II clinical trial in patients with liver cancer that cannot be treated with surgery and whose cancer has failed to respond to the existing standard treatments. The trial began in August at sites in Spain and Italy.
“NMS-01940153E represents a new type of treatment, working in a very different way from the current options for treating liver cancer; therefore, it offers potential to help patients in the future,” said Reig. “This is a small study, so the results will need to be shown in larger studies. The strength of the study is that the effect of NMS-01940153E appears to be realistic, due to the history of prior treatment failures of these patients and the early pattern of response we observed.”
