AB Science has announced results from a phase 2 study with its investigational drug, masitinib, in imatinib-resistant gastrointestinal stromal tumours (GIST).

Masitinib significantly improved overall survival in patients with imatinib-resistant gastrointestinal stromal tumours (GIST) as compared to sunitinib from Pfizer, a drug approved for second-line treatment of GIST, currently the standard of care for these patients.

In this study, 44 patients with inoperable, locally advanced or metastatic GIST and showing disease progression while treated with imatinib (400 to 800 mg/day) received either masitinib (23 patients) at 12 mg/kg/day or sunitinib (21 patients) until progression.

After a median follow-up of 14 months, median overall survival was not reached for masitinib versus 15 months for sunitinib (p=0.022 HR:3.2).

After 18 months, 79% of patients treated with masitinib were still alive, versus 20% for patients treated with sunitinib.

After 2 years, 53% of patients treated with masitinib were still alive, versus 0% for the patients treated with sunitinib. The study also demonstrated that masitinib was significantly better tolerated than sunitinib.

The safety profile of masitinib was better than that of sunitinib, with a significantly longer Safety Event Free Survival (p=0.002), and a lower occurrence of severe adverse events. In masitinib treated patients, nausea, diarrhea and asthenia were the most common related adverse events.

Full data has been submitted for publication to the American Society of Clinical Oncology (ASCO) 2012 Annual Meeting. Axel Le Cesne, MD (Institut Gustave Roussy, France), the principal investigator of this study declared: “Given this substantial advantage in survival coupled with lower toxicity of masitinib as compared with Sunitinib, we believe that masitinib is an important step forward in the treatment of GIST.” Olivier Hermine, MD, PhD, President of the Scientific Committee of AB Science commented: “Masitinib differs from sunitinib by its selectivity profile.

Unlike sunitinib, which targets a broad spectrum of protein kinases, masitinib is very selective, which brings better tolerability. Furthermore, in addition to killing cells that make up the tumours, masitinib has a complementary mode of action that may also kill cancer stem cells and trigger an immune response, which may further enhance its efficacy. These promising results in second line treatment of GIST, which correlate with the encouraging results previously reported in the first line treatment of GIST, tend to confirm that masitinib has an original mechanism of action that may translate into improved survival.”

Gastrointential stromal tumour (GIST) is a sarcoma, which is a type of cancer that develops in the cells of the body’s connective or supportive tissues. GIST arises within the gastrointestinal tract. It is estimated that approximately 5,000 to 6,000 new patients are diagnosed with GIST each year in the United States.

In 2010, the global GIST therapeutics market was valued at $920 million, and forecast to grow at a rate of 2% annually. Masitinib received orphan drug designation in the treatment of GIST from both the FDA and EMA. About masitinib Masitinib is an investigational orally administered tyrosine kinase inhibitor that targets mast cells, important cells for immunity, as well as a limited number of kinases that play key roles in various cancers.

Owing to its novel mechanism of action, masitinib can be developed in a large number of conditions in oncology, inflammatory diseases and certain diseases of the central nervous system. Through its activity of inhibiting certain kinases that are essential in some oncogenic processes, masitinib may have an effect on tumour regression, alone or in combination with chemotherapy.

Through its activity on the mast cell and certain kinases essential to the activation of the inflammatory cells and fibrosing tissue remodeling, masitinib can have an effect on the symptoms associated with some inflammatory and central nervous system diseases.

Source: AB Science