ARIAD Pharmaceuticals initiates ponatinib Phase 2 trial in adult patients with metastatic GIST

ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced the initiation of the Phase 2 trial of Iclusig^® (ponatinib) in adult patients with metastatic and/or unresectable gastrointestinal stromal tumors (GIST). The trial is designed to provide initial clinical data evaluating the efficacy and safety of ponatinib in patients with GIST following failure of prior tyrosine kinase inhibitor (TKI) therapy.

“Patients with GIST have limited treatment options following development of resistance to TKI therapy, and we are pleased to work with leading clinical research sites to investigate ponatinib as a new treatment for these patients.”

"This trial represents an important step in ponatinib's expanded clinical development beyond Philadelphia-positive leukemias and into solid tumors. KIT is a clinically validated oncogenic target for GIST and is known to drive approximately 85 percent of these cancers. In preclinical studies ponatinib was highly potent against activated KIT and most of its resistance mutants," stated Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer of ARIAD. "Patients with GIST have limited treatment options following development of resistance to TKI therapy, and we are pleased to work with leading clinical research sites to investigate ponatinib as a new treatment for these patients."

Trial Design

The Phase 2 trial is an open-label, multicenter trial to evaluate the efficacy and safety of ponatinib in patients with metastatic and/or unresectable GIST after prior failure of at least one TKI. Patients whose tumors have an activating mutation in exon 11 of cellular KIT, the primary driver for patients with GIST and KIT mutations, will be enrolled in Cohort A. Patients whose tumors have other activating mutations will be enrolled into Cohort B. The trial will be conducted at three investigational sites in the United States: Dana Farber Cancer Institute, Fox Chase Cancer Center and Oregon Health Science University.

A total of approximately 45 patients will be enrolled in the trial, with at least 30 patients in Cohort A. Patients will receive the same dose of ponatinib, 45 mg administered orally once daily, as used in patients with Philadelphia-positive leukemias.

The Clinical Benefit Rate (CBR), measuring disease control and defined as the composite of complete response, partial response, and stable disease lasting 16 weeks or more, is the primary endpoint for the trial and will be analyzed in Cohort A. Secondary endpoints will include progression-free survival, objective response rate, overall survival, safety and pharmacokinetic parameters.