ASCO 2014: Results of the dose-escalation portion of a phase 1/2 study (CHAMPION-1) investigating weekly carfilzomib in combination with dexamethasone for patients with relapsed or refractory multiple myeloma

Jun 23, 2014

Abstract No: 8594

Background: Carfilzomib (CFZ) is a selective proteasome inhibitor approved in the US for the treatment of relapsed and refractory multiple myeloma (MM). This multicenter, single-arm phase 1/2 study (NCT01677858) is evaluating the safety and efficacy of once-weekly CFZ with dexamethasone (DEX).

Methods: Patients (pts) with relapsed or refractory MM who received 1−3 prior regimens were eligible. Pts received CFZ as a 30-minute IV infusion on days (D) 1, 8, and 15 of a 28-day cycle in a standard 3+3 dose-escalation scheme. All pts received CFZ at 20 mg/m2 on D1 of cycle 1; subsequent doses started at 45 mg/m2 and were escalated to 56, 70, or 88 mg/m2in successive cohorts until the maximum tolerated dose (MTD) was reached. Pts received 40 mg DEX (IV or oral) on D1, 8, 15, and 22 of cycles 1–8; DEX was omitted on D22 in cycles ≥9. Response was assessed by IMWG criteria; minimal response (MR) was assessed by EBMT criteria. The primary objective of the phase 1 portion of the study was to determine the MTD.

Results: As of 11/5/2013, 27 pts were enrolled (median age, 64 years [range, 43–84]; median prior regimens, 1 [range, 1–3]). At 88 mg/m2, 2 dose-limiting toxicities (DLTs) were observed: grade [Gr] 3 dyspnea and Gr 3 vomiting. At the MTD (70 mg/m2), 1 patient of 15 experienced a DLT (Gr 3 dyspnea). Gr ≥3 AEs reported in >1 pt were thrombocytopenia, increased blood creatinine, dyspnea, and hyperglycemia (n=2 each; all Gr 3). No Gr ≥3 peripheral neuropathy was reported. All 27 pts were included in the preliminary efficacy evaluation. The overall response rate (ORR; ≥partial response) was 63% and the clinical benefit rate (CBR; ≥MR) was 74%. At the MTD, the ORR was 60% and the CBR was 67%. Pharmacokinetic analysis (n=21) showed a dose-dependent increase in mean Cmax and AUC for 20–88 mg/m2CFZ. The mean terminal half-life was ~0.8 hours.

Conclusions: At the MTD, weekly CFZ with DEX had an acceptable safety and tolerability profile with promising efficacy after a short follow-up period in pts with relapsed or refractory MM. The phase 2 portion of the study is currently enrolling pts at 70 mg/m2 CFZ. Updated results from the phase 1/2 study will be presented.

Clinical trial information: NCT01677858.

Author(s): James R. Berenson, Leonard M. Klein, Robert M. Rifkin, Priti Patel, Sandra Dixon, Ying Ou, Alan Cartmell; Institute for Myeloma and Bone Cancer Research, West Hollywood, CA; Illinois Cancer Specialists, Niles, IL; US Oncology Research, Inc., Denver, CO; Onyx Pharmaceuticals, Inc, South San Francisco, CA; Comprehensive Blood and Cancer Center, Bakersfield, CA

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