Amgen (NASDAQ: AMGN) today announced the initiation of the ARROW trial, a global Phase 3 study evaluating the benefit of Kyprolis® (carfilzomib) for Injection administered once-weekly with dexamethasone versus the current U.S. Food and Drug Administration (FDA) approved twice-weekly administration schedule in patients with relapsed and refractory multiple myeloma who have received prior treatment with bortezomib and an immunomodulatory agent (IMiD). The trial was initiated based on results from the Phase 1/2 CHAMPION study, which were presented (abstract no. 8527) at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) on Sunday, May 31 at 8 a.m. CT.
Results from the Phase 1 and 2 portions of CHAMPION were presented for 104 patients (Phase 1, n=15; Phase 2, n=89) with relapsed or refractory multiple myeloma who had received one to three prior treatment regimens at the determined maximum tolerated dose (MTD) of 20/70 mg/m2. In the Phase 2 portion of the study, the overall response rate (ORR; defined as the percentage of patients achieving a partial response or better) was 77 percent. The clinical benefit rate (CBR; defined as the percentage of patients with minimal response or better) was 84 percent; the median time to response for patients who achieved a partial response or better was 1.6 months (range, 0.7-7.2); Kaplan-Meier median duration of response (DOR) was 15 months (95 percent CI 9-not estimable); and the Kaplan-Meier median progression-free survival (PFS) was 10.6 months (95 percent CI 9.0-16.1).
"The results from the CHAMPION Phase 1/2 study form the basis of the Phase 3 ARROW study with the goal of potentially providing patients and physicians greater convenience with a once-weekly dosing schedule of Kyprolis," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "The initiation of this trial underscores our commitment to addressing the needs of patients with multiple myeloma through the entire treatment continuum."
The most common hematologic treatment-emergent adverse events (AEs) of any grade were anemia (24 percent), thrombocytopenia (22 percent) and neutropenia (8 percent). The most common non-hematologic treatment-emergent AEs of any grade were fatigue (52 percent), nausea (35 percent), headache and diarrhea (31 percent each). The most commonly occurring grade ≥3 hematologic treatment-emergent AEs were thrombocytopenia (6 percent), anemia (5 percent) and neutropenia (4 percent). The most common non-hematologic grade ≥3 treatment-emergent AEs were fatigue (11 percent), pneumonia (7 percent), acute renal failure and hypertension (6 percent each). Adverse events grade ≥3 included cardiac failure (2 percent) and peripheral neuropathy (1 percent).
A total of 36 patients (35 percent) had at least one serious AE. Sixteen patients (15 percent) treated at the MTD had at least one carfilzomib dose reduction due to AEs, and 10 patients (10 percent) discontinued study treatment due to AEs. Ten patients (10 percent) discontinued treatment due to investigator's discretion, 12 patients (12 percent) discontinued due to patient decision and 34 patients (33 percent) discontinued due to progressive disease. A total of five patients died during the study, all of which were in the Phase 2 portion of the study: one patient each had cause of death reported as cardiopulmonary arrest, pneumonia, disease progression, acute respiratory distress syndrome and acute kidney injury.