Background: KRd is approved for treatment of RRMM patients (pts). Under the approved KRd regimen, carfilzomib is given twice weekly (20/27 mg/m²; 10-min IV infusion). Here we present updated results from a dose-finding study assessing weekly KRd. Methods: This study consisted of a dose-evaluation component and a dose-expansion component in both RRMM and newly diagnosed MM. Results for RRMM pts are presented here. Two dose levels were evaluated: carfilzomib 56 mg/m² and carfilzomib 70 mg/m². All pts received carfilzomib (30-min IV infusion on days [D] 1, 8, and 15; 20 mg/m² on C1D1), lenalidomide 25 mg (D1–21), and dexamethasone 40 mg (D1, 8, 15, and 22) on a 28-day cycle (dexamethasone was not given on D22 for cycles 9+). Pts in the expansion arm received the selected KRd regimen on the same schedule used for dose evaluation. Response was assessed by investigators. Results: Twenty-two RRMM pts were enrolled in the dose-evaluation part and received study drug (56 mg/m², n = 10; 70 mg/m², n = 12). The maximum tolerated dose of carfilzomib was not reached; the 70 mg/m² dose was selected for dose expansion and 34 additional RRMM pts received this dose. Results are presented for pts who received carfilzomib 56 mg/m² during dose evaluation (n = 10; median 2 prior regimens [range 1-3]) and for pts who received carfilzomib 70 mg/m² during dose evaluation or expansion (n = 46; median 1 prior regimen [range 1-5]). Median (mean) average carfilzomib dose was 53.2 (52.8) mg/m² in the 56 mg/m² group and 62.4 (61.3) mg/m² in the 70 mg/m² group. Pt incidence of grade ≥3 adverse events was 70.0% (56 mg/m²) and 71.7% (70 mg/m²). Pt incidence of carfilzomib discontinuation due to adverse events was 20.0% (56 mg/m²) and 17.4% (70 mg/m²). There were three total deaths in the 70 mg/m² group (one each due to cardiac arrest, cardiac disorder, and progressive disease). Overall response rates were 90.0% (56 mg/m²) and 89.1% (70 mg/m²); 20.0% (56 mg/m²) and 30.4% (70 mg/m²) of pts achieved a complete response (CR) or stringent CR. Conclusions: Once weekly KRd was effective and had manageable toxicity in pts with RRMM. As a weekly carfilzomib dosing regimen could offer pts greater convenience, these results support further clinical evaluation. Clinical trial information: NCT02335983