New combination trial for GIST: imatinib plus MEK inhibitor MEK162
A new clinical trial opened in November 2013 at Memorial Sloan-Kettering Cancer Center to test the combination of imatinib (Gleevec) plus MEK162, an inhibitor of the MEK pathway.
Principal investigator Ping Chi, MD PhD and William Tap, MD discuss the trial and its rationale in this short video you can watch.
Groundbreaking research by Chi and colleagues identified transcription factor ETV1 as necessary for GIST growth and survival. ETV1 is activated downstream of KIT via the MAPK pathway and can be targeted using an inhibitor of MEK. You can access the free full text of the background research paper at this link.
The trial is open only to patients with measurable metastatic or advanced GIST who have received no drug therapies other than adjuvant imatinib. The initial Phase Ib arm of the trial will identify the appropriate tolerable dose of MEK162 to be used in combination with 400 mg of imatinib. In the Phase II portion of the trial patients will receive imatinib plus MEK162 until disease progression.
The hope is that this combination therapy will be more effective than imatinib alone, potentially causing greater tumor cell death and longer duration of disease control without development of imatinib resistance.