James Berenson¹, Roger m. Lyons², Wael Harb³, DimitriosTzachanis⁴, Ralph Boccia⁵, Robert m. Rifkin⁶, Priti Patel⁷, Jesus Berdeja⁸

¹Department of Oncology, Institute for Myeloma and Bone Cancer Research, ²Department of Medical Oncology, US Oncology and Cancer Care Centers of South Texas, ³Department of Medical Oncology, Horizon Oncology Center, ⁴Department of Blood and Marrow Transplant, Cedars-Sinai Medical Center, ⁵Department of Medical Oncology, Center for Cancer and Blood Disorders, ⁶Department of Medical Oncology, US Oncology Research Inc., ⁷Inc., Onyx Pharmaceuticals, ⁸Department of Myeloma Research, Sarah Cannon Research Institute.

Objective:Carfilzomib (K) is a selective proteasomeinhibitor that is approved in the United States for the treatment of relapsedand refractory multiple myeloma. Here we present updated results fromCHAMPION-1: a multicenter, single-arm, phase 1/2 study evaluating the safetyand efficacy of weekly K with dexamethasone (DEX; Kd) in patients (pts) withrelapsed or refractory multiple myeloma (RRMM). Method: Pts who received1−3 prior regimens were eligible. In the phase 1 portion, pts received K(30-min IV infusion) on days (D) 1, 8, and 15 of a 28-day cycle in a 3+3dose-escalation scheme. All pts received K at 20mg/m² on D1 of cycle1; subsequent dose cohorts received 45, 56, 70, or 88mg/m²successively until the maximum tolerated dose (MTD) was reached. Pts receivedDEX 40mg (IV or PO) on D1, 8, 15, and 22 of cycles 1-8; DEX was omitted on D22in cycles ≥9. In the phase 2 portion, pts are receiving K at the MTD with thesame dose and schedule for DEX. Kd is administered until progressive disease(PD) or unacceptable toxicity. Result: s are presented for pts treatedat the MTD (70mg/m²) in the phase 1 and phase 2 portions of thestudy. As of January 7, 2015, 104 pts (phase 1, n=15; phase 2, n=89 pts) wereenrolled at the MTD; the study is fully enrolled. Median pt age was 68.5 years(range, 41-88). Pts received a median of 1 prior regimen (range, 1-3).Preliminary median K treatment duration was 5.3 months (range, 0.03-18.8). Theoverall response rate (≥ partial response) was 72% (95% confidence interval[CI]: 63%-81%). Kaplan-Meier median PFS was 10.6 months (95% CI: 7.2-notestimable). The most common all-grade adverse events (AEs) were fatigue (48%),nausea (32%), and insomnia (30%). The most common grade ≥3 AEs were fatigue(9%) and thrombocytopenia, dyspnea, and back pain (6% each); 7 pts (7%)discontinued treatment due to AEs. Four pts died on study: 1 pt had sepsis,respiratory distress, pneumonia, and acute renal failure; and 1 pt each hadacute renal failure, cardiopulmonary arrest, and PD. Conclusion: At theMTD (70 mg/m²), weekly Kd is demonstrating acceptable safety andtolerability with promising efficacy in pts with RRMM.

Key Words: Carfilzomib, Multiplemyeloma