Merck and Vertex Pharmaceuticals, Inc. began an international Phase II trial of MK-0457 (also known as VX-680), a small molecule inhibitor of Aurora, FLT-3, JAK-2 and BCR-ABL kinases. The study will be conducted in patients with treatment-resistant chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphocytic leukemia (Ph+ ALL) containing the T315I BCR-ABL mutation. With the start of dosing, Vertex earned a $25 million milestone payment from Merck.
"This pivotal trial based on a population prospectively defined by a genetic marker will hopefully represent a new paradigm for development of drugs targeting specific cancer patient populations," said Stephen H. Friend, M.D., Ph.D., executive vice president and franchise head, oncology and neuroscience, Merck Research Labs. "MK-0457 is the first compound to show clinical activity in patients with certain treatment-resistant forms of blood cancers. Based on encouraging Phase I results reported recently at the American Society of Hematology meeting, we are moving forward with this international Phase II trial in these patients."
Merck will conduct the trial of MK-0457, which is expected to enroll approximately 270 adult patients with advanced CML and ALL leukemias harboring the T315I BCR-ABL mutation. MK-0457 will be given as a five-day intravenous infusion every two-to- three weeks to evaluate safety and efficacy. Merck may seek marketing approval for MK-0457 based on the data generated in this trial. The study has been designed to support registration of MK-0457 in one or more cancer indications for which there is currently little or no effective treatment.