A Phase I clinical trial for a potential new mesothelioma drug, conducted in nine cancer centers in France, Australia, and the United Kingdom, is showing great promise, the study’s lead author proclaimed at the recent 24th annual EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Dublin, Ireland.
According to a press release by the European Cancer Organization (ECCO), the drug – known as GSK226098 – showed considerable success in preventing the spread of asbestos-caused cancer in patients who were lacking an active tumor suppressor gene called NF2.
“Previous research has shown that the gene NF2, which produces a protein called merlin, is frequently inactivated in approximately 50% of mesotheliomas,” explained the report of the study results. “Merlin negatively regulates another protein called focal adhesion kinase (FAK) in mesothelioma, and so when NF2 and merlin are inactivated, the activity of FAK is increased and mesothelioma cells become invasive and start to spread. When NF2 and merlin activity is restored, FAK activity and cell invasion are decreased.”
The drug, explains Professor Jean-Charles Soria, Professor of Medicine and Medical Oncology at South Paris University and head of early drug development at the Institut Gustave Roussy in Paris, is designed to inhibit FAK and, therefore, stop – or at least slow – the spread of the disease, which is normally very aggressive and rarely responds positively to current treatment options.
“Early in the clinical study presented today, a patient with mesothelioma, who had progressed quickly on prior therapies, had prolonged stable disease while on GSK2256098, which is suggestive of clinical activity,” stressed Soria.
The 29 mesothelioma patients were given the drug orally in capsule form twice a day, the press release reports. “In patients in whom merlin was inactivated, the average time before the disease progressed was 24 weeks, compared to 11 weeks in patients with active merlin and nearly 11 weeks in patients in whom the activity of merlin was unknown,” the study results stated. No one reported any intolerable side effects from the drug.
“These findings are important but preliminary,” said Soria. “They show that merlin is a potential biomarker in mesothelioma that may enable us to identify a subset of patients who could benefit from GSK2256098 and have longer, progression-free survival. Mesothelioma is a deadly disease without many treatment options, and therefore identification of novel and effective therapies is needed.”