The study will investigate the safety, tolerability, pharmacokinetics and preliminary efficacy of INNO-406 in adult patients with Gleevec-resistant or intolerant Philadelphia positive (Ph+) leukemia or relapsed/refractory Ph+ acute lymphocytic leukemia (ALL).
The trial is expected to enroll up to 100 patients at the MD Anderson Cancer Center in Texas and the Johann Wolfgang Goethe University Hospital in Germany.
INNO-406 is an orally bioavailable, rationally designed, dual Bcr-Abl and Lyn kinase inhibitor. According to a study published in the journal Blood, INNO-406 is 25 to 55 times more potent than imatinib (the active ingredient in Novartis’ Gleevec) in vitro, and at least 10 times as effective as imatinib mesylate in suppressing the growth of Bcr-Abl bearing tumors in vivo.
INNO-406 has demonstrated activity against 12 of 13 Gleevec-resistant cell lines with point mutations of the Bcr-Abl protein. Research is ongoing to determine activity in other known point mutations.
In addition to its Bcr-Abl inhibitory properties, INNO-406 inhibits Lyn kinase. Upregulation of Lyn kinase activity is a well-recognized cause of imatinib resistance. Lyn kinase activation has also been documented in a variety of solid tumors, including prostate cancer.
“There is a pressing demand for new treatment options for CML. INNO-406 shows excellent potential because of its potent inhibition of Bcr-Abl and its specificity for Lyn which could contribute to a unique efficacy and toxicity profile,” said Dr Hagop Kantarjian, chairman of the department of leukemia at the MD Anderson Cancer Center and principal investigator of the INNO-406 trial at that site.