ARIAD Pharmaceuticals, Inc. (NASDAQ:ARIA) today announced, for the first time, data from its Phase 2 trial of Iclusig® (ponatinib) in adult patients with refractory metastatic and/or unresectable gastrointestinal stromal tumors (GIST). The initial data show that ponatinib has anti-tumor activity in patients with advanced GIST, particularly in patients with KIT exon 11 mutations, after failure of at least one prior tyrosine kinase inhibitor (TKI). The primary endpoint for the trial, clinical benefit rate (CBR) at 16 weeks for patients with KIT exon 11 mutations, was 50 percent, with a median follow-up of six months.
These data are being featured today in an oral presentation at 10:00 a.m. CT at the Annual Meeting of the American Society of Clinical Oncology (ASCO) being held in Chicago.
The Phase 2 trial of ponatinib in GIST enrolled 35 patients as of April 7, 2014. The trial is ongoing, and the FDA partial clinical hold to new patient enrollment has been lifted. The patient population in the trial is heavily pre-treated, with 46 percent having failed three prior GIST-approved TKIs. Patients were enrolled into two cohorts based on the presence (Cohort A) or absence (Cohort B) of KIT exon 11 mutations. Primary KIT mutations occur in approximately 85 percent of patients with GIST. The most common mutation is on exon 11 (~70 percent). Preclinically, ponatinib showed compelling activity against activating exon 11 mutations.
"These initial data support the preclinical findings that ponatinib has activity against the acquired mutations in KIT which patients with GIST can develop following treatment with other targeted TKIs," stated Michael C. Heinrich, M.D., professor of medicine and cell/developmental biology at the Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon. "Treatment with approved agents in the second or third-line settings is associated with a median time to progression of less than six months for each line of treatment. There is a great unmet need for additional treatments for this population of patients. Stable disease at 16 weeks is an important milestone for refractory patients so I believe these early clinical responses to ponatinib are encouraging."
ARIAD Pharmaceuticals, Inc.,