The phase III FOCUS clinical trial of Kyprolis in multiple myeloma did not meet its primary endpoint of improving overall survival.
The 315-patient, open-label study evaluated Kyprolis (carfilzomib) for Injection compared to an active control regimen of low-dose dexamethasone, or equivalent corticosteroids, plus optional cyclophosphamide in patients with relapsed and advanced refractory multiple myeloma.
Nearly all patients in the control arm received cyclophosphamide. Patients were heavily pretreated and had received a median of five therapeutic regimens prior to study entry. Detailed results will be submitted for presentation at an upcoming scientific meeting.
Secondary trial endpoints included progression-free survival, overall response rate, clinical benefit rate, duration of response and safety.
Patients were randomized to receive Kyprolis (20mg/m(2) on days 1 and 2 of cycle 1 followed by 27mg/m(2) on days 8, 9, 15, and 16 of cycle 1 and all doses cycle 2 through 9, and 27 mg/m(2) on days 1,2,15, and 16 of cycle 10 and beyond) or an active control regimen of oral steroids and optional cyclophosphamide.
Treatment discontinuation due to adverse events and on-study deaths were comparable between the two arms. There was an increase in the incidence of renal adverse events of all grades observed in the Kyprolis arm compared to the active control arm and the label. The rate of cardiac events observed in the Kyprolis arm was consistent with the current U.S. Kyprolis label.
In July 2012, FDA granted accelerated approval to Kyprolis for Injection for multiple myeloma patients who have received at least two prior therapies including bortezomib and an immunomodulatory agent, and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval was based on response rate. Clinical benefit, such as improvement in survival or symptoms, has not been verified.
Kyprolis is marketed in the U.S. by Onyx Pharmaceuticals, an Amgen subsidiary.
