Date: 2014-08-13
Type of information: Results
phase: 3
Announcement: results
Company: Amgen (USA - CA)
Product: Kyprolis® (carfilzomib)
Action
mechanism: proteasome inhibitor. Carfilzomib is a selective proteasome inhibitor.
Disease: relapsed and advanced refractory multiple myeloma
Therapeutic area: Cancer - Oncology
Country:
Trial
details: The randomized, open-label Phase 3 FOCUS (CarFilzOmib for AdvanCed Refractory MUltiple Myeloma European Study) trial evaluated single-agent Kyprolis® versus an active control regimen of low-dose steroids plus optional cyclophosphamide in patients with relapsed and advanced refractory multiple myeloma following treatment with at least three prior therapies. The primary endpoint of the trial was overall survival. Secondary endpoints included progression-free survival, overall response rate, clinical benefit rate, duration of response and safety. Patients were randomized to receive Kyprolis (20mg/m2 on days 1 and 2 of cycle 1 followed by 27mg/m2 on days 8, 9, 15, and 16 of cycle 1 and all doses cycle 2 through 9, and 27 mg/m2 on days 1,2,15, and 16 of cycle 10 and beyond) or an active control regimen of oral steroids and optional cyclophosphamide. The trial enrolled 315 patients.
Latest
news: * On August 13, 2014, Amgen and its subsidiary, Onyx Pharmaceuticals, announced that the Phase 3 clinical trial FOCUS (CarFilzOmib for AdvanCed Refractory MUltiple Myeloma European Study) did not meet its primary endpoint of improving overall survival (OS) (HR=0.975, 95 percent CI, 0.760, 1.249). The 315-patient, open-label study evaluated single-agent 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.
Treatment discontinuation due to adverse events and on-study deaths were comparable between the two arms. The rate of cardiac events observed in the Kyprolis® arm was consistent with the current U.S. Kyprolis® label. 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.
On July 20, 2012 , the FDA granted accelerated approval of Kyprolis® for Injection for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory agent (IMiD), 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.
