Date: 2014-07-28
Type of information: Publication of results in a medical journal
phase: 2
Announcement: publication of results in the Annals of Oncology
Company: AB Science (France)
Product: masitinib
Action
mechanism: kinase inhibitor/tyrosine kinase inhibitor. Masitinib is a 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.
Disease: Gleevec®-resistant gastrointestinal stromal tumor (GIST)
Therapeutic area: Cancer - Oncology - Rare diseases
Country:
Trial details:
Latest
news: * On July 28, 2014, AB Science announced the publication of results from a randomized phase 2 study of masitinib in treatment of Gleevec®-resistant gastrointestinal stromal tumor. Entitled, ‘Masitinib in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib: a randomized controlled open-label trial’ this article has been published in the peer-reviewed journal Annals of Oncology: An international phase 3 trial of masitinib in patients with Gleevec®-resistant/intolerant GIST has been initiated based on these results. The objectives of this study are to reaffirm that masitinib has a superior safety profile to that of sunitinib in this population and also to confirm the observed survival benefits of administering masitinib in the second-line setting. This study will enroll approximately 208 patients (104 patients per treatment-arm). The primary response evaluation will be overall survival.
- Findings showed masitinib to produce a statistically significant overall survival (OS) advantage of 12.4 months in patients with Gleevec®-resistant GIST when compared with Sutent® (sunitinib) from Pfizer, which is currently the standard of care for second-line treatment of advanced GIST.
- Overall, encouraging survival and safety data from a well-controlled and appropriately designed randomized trial indicate a positive benefit–risk balance.
- Primary efficacy analysis ensured the masitinib treatment arm could satisfy a prespecified progression-free survival (PFS) threshold. Secondary efficacy analysis showed that masitinib followed by the standard of care generated a statistically significant survival benefit over standard of care.
- An international phase 3 trial of masitinib in patients with Gleevec®-resistant/intolerant GIST has been initiated based on these promising results.
Reported are results of a phase 2 study conducted by Professor Axel Le Cesne (Institut Gustave, Villejuif, France) and colleagues from nine study centers across France. In this study, 44 patients with inoperable, locally advanced or metastatic GIST and showing disease progression while treated with Gleevec® (imatinib) (400 to 800 mg/day) received either masitinib (23 patients) at 12 mg/kg/day or sunitinib (21 patients) at 50 mg/day until progression. The study met its primary analysis end point, namely, that the
lower bound of the 90% unilateral confidence interval for median PFS (central RECIST) was above a threshold of 3 months for the masitinib treatment arm. Because the primary analysis hypothesis test was conclusive with masitinib, the study was considered a success and further analyses were warranted to evaluate masitinib efficacy and safety. As a secondary analysis, masitinib followed by the standard of care showed a statistically significant survival benefit with respect to standard of care (hazard ratio = 0.27 [0.09–0.85]). Additionally, the safety profile of masitinib was better than that of sunitinib, as evidenced by masitinib-treated patients experiencing less toxicity and reporting a longer time until definite quality of life deterioration.
