SINGLE-AGENT CARFILZOMIB VERSUS A BEST SUPPORTIVE CARE REGIMEN IN PATIENTS WITH RELAPSED AND REFRACTORY MULTIPLE MYELOMA: FOCUS (PX-171-011), A RANDOMIZED, OPEN-LABEL, PHASE 3 STUDY

Sborník

Background. The proteasome inhibitor carfilzomib has demonstrated singleagent activity in phase 2 studies in patients with relapsed and refractory multiple myeloma (R/R MM). In PX-171-003-A1 “ ‘a single-arm study of carfilzomib monotherapy in heavily pretreated refractory patients” ’37% of patients achieved > minimal response (MR), median time to progression was 3. 9 months, and median overall survival (OS) was 15. 5 months. Carfilzomib is currently under review by the US Food and Drug Administration for approval to treat R/R MM. Aims. Herein we describe the trial design and rationale for a phase 3 randomized study, FOCUS (CarFilzOmib for AdvanCed Refractory MUltiple Myeloma European Study), being conducted to compare OS after treatment with singleagent carfilzomib to a “best supportive care”(BSC) regimen (low-dose glucocorticoids with optional cyclophosphamide, plus comfort and palliative care). Methods. Patients must have received ≥3 prior regimens including bortezomib treatment (defined as ≥4 cycles at full dose as tolerated). Patients must have been responsive to ≥1 line of therapy and be either nonresponsive (≤ stable disease) or refractory to their most recent therapy. Eligible patients are randomized 1:1 (stratified by number of previous therapies and geographical region) to carfilzomib or BSC regimen. Target enrollment is 302 patients. Treatment schemes are:Treatment will continue until disease progression or unacceptable toxicity. Following confirmation of disease progression or discontinuation from study treatment, all patients will enter long-term follow-up for survival. Crossover is not allowed upon progression. The primary endpoint is OS, and secondary endpoints include progression-free survival, overall response rate, clinical benefit rate, disease control rate, duration of response, and safety. Disease assessments will be determined by study investigators and an independent review committee according to the International Myeloma Working Group Uniform Response Criteria (with MR per European Blood and Marrow Transplantation Group criteria). FOCUS began accruing patients in September 2010, and 141 patients are enrolled as of the end of January 2012. Conclusions. FOCUS will provide more rigorous data for carfilzomib, as this is the first carfilzomib study with OS as the primary endpoint and it will not be confounded by crossover. The larger study group will also provide more robust secondary response and safety results that will add to the data set from prior phase 2 studies. This phase 3 study of carfilzomib monotherapy for patients with R/R MM 17th Congress of the European Hematology Association will provide important information necessary to facilitate regulatory approvals around the world and to expand treatment options to meet the unmet need of these patients with advanced disease.

Haematologica, 2012; 97(s1):  614