Background: Carfilzomib (K) is a selective proteasome inhibitor that is approved for the treatment of relapsed and refractory multiple myeloma in the US. CHAMPION-1 (NCT01677858) is a multicenter, single-arm, phase 1/2 study evaluating the safety and efficacy of weekly K with dexamethasone (dex; Kd) in pts with RRMM. Methods: Pts who received 1−3 prior regimens were eligible. In the phase 1 portion, pts received K as a 30-min IV infusion on days 1, 8, and 15 of a 28-day cycle using a 3+3 dose-escalation scheme. Pts received K at 20 mg/m² on day 1 of cycle 1; subsequent doses started at 45 mg/m² and were escalated to 56, 70, or 88 mg/m² until the maximum tolerated dose (MTD) was reached for use in the phase 2 portion. Pts received dex 40 mg (IV or oral) on days 1, 8, 15, and 22 of cycles 1–8; dex was omitted on day 22 in cycles ≥ 9. Kd was administered until disease progression or unacceptable toxicity. Results: The MTD was reported previously (70 mg/m²). As of January 7, 2015, 104 pts were enrolled at the MTD (phase 1, n = 15; phase 2, n = 89). Median pt age was 68.5 y (range, 41–88). Pts received a median of 1 prior regimen (range, 1–3); 82% of pts had received prior bortezomib (BTZ). A total of 48% of pts were BTZ-refractory, 28% were lenalidomide (LEN) refractory, and 16% were refractory to BTZ and LEN. Preliminary median K treatment duration in the ongoing study was 5.3 mo (range, 0.03–18.8). The overall response rate ( ≥ partial response) was 72% (95% confidence interval [CI]: 63%–81%); the clinical benefit rate ( ≥ minimal response) was 80% (95% CI: 71%–87%). Median PFS was 10.6 mo (95% CI: 7.2–not estimable). Seven pts (7%) discontinued treatment due to an adverse event (AE). The most common grade ≥ 3 AEs were fatigue (9%), thrombocytopenia (6%), dyspnea (6%), back pain (6%), anemia (5%), and acute renal failure (5%). Four pts died on study: 1 pt had sepsis, respiratory distress, pneumonia, and acute renal failure; and 1 pt each had acute renal failure, cardiopulmonary arrest, and disease progression. Conclusions: At the MTD (70 mg/m²), weekly Kd had acceptable safety and tolerability with promising efficacy in pts with RRMM. Updated results will be presented at the meeting. Clinical trial information: NCT01677858