Clinical data from a phase Ib combination trial, in which KOS-953 was administered with bortezomib (Millennium’s Velcade), also showed signs of anti-myeloma activity in bortezomib-naive and -refractory patients.
Both trials are open-label, dose-escalation studies designed to determine the maximum tolerated dose, safety profile, pharmacokinetics and recommended phase II dose of KOS-953 when given as a single agent or in combination with bortezomib. In both trials, KOS-953 was administered at escalating dose levels on a twice-weekly schedule every three weeks. In the combination trial, this treatment was preceded by administration of bortezomib.
In the single-agent trial, 64% of the evaluable patients showed either partial response, minor response, or stable disease. In the combination trial, 66% of the evaluable patients showed either a minor response or stable disease.
Side effects were manageable and similar for the two trials, including gastrointestinal effects, anemia, rash, myalgias/muscle cramps, and fatigue. Thrombocytopenia was also observed in the combination trial. Dose escalation in both studies is continuing in order to define the recommended dose for future trials.
“We are encouraged by these results demonstrating anti-myeloma activity of KOS-953 in heavily pretreated patients, both as single-agent and in combination with bortezomib,” said Dr Robert Johnson, Jr, Kosan’s executive vice president of development and chief medical officer. “Our plan is to continue these trials to their protocol-defined endpoints, defining a tolerable dose with signs of biological activity, with the expectation of moving to larger phase II trials in myeloma.”