The second-generation proteasome inhibitor carfilzomib produces superior outcomes in relapsed or refractory multiple myeloma (MM). We conducted a single-arm trial of twice-weekly carfilzomib (27 mg/m(2))-dexamethasone (Kd27) for relapsed and refractory MM in China. Kd27 was administered in 28-day cycles to 123 patients previously treated with >= 2 other regimens, including treatment with bortezomib and an immunomodulatory drug, and refractory to their most recent therapy. Overall response rate (ORR) was the primary endpoint; progression-free survival (PFS) and overall survival (OS) were key secondary endpoints. Primary analysis was conducted when all patients received >= 6 cycles of Kd27 or discontinued Kd27. Median age was 60 years; median number of prior regimens was 4; 74% were refractory to proteasome inhibitors and immunomodulatory drugs. ORR was 35.8% (95% CI 27.3-44.9), median PFS was 5.6 (95% CI 4.6-6.5) months, and median OS was 16.6 (95% CI 12.2-NE) months. Grade >= 3 adverse events (AEs) occurred in 76.4% of patients. Grade >= 3 AEs of interest included hypertension (13.8%), acute renal failure (3.3%), cardiac failure (0.8%), ischemic heart disease (0.0%), and peripheral neuropathy (0.0%); 5.7% of patients discontinued carfilzomib due to AEs. Carfilzomib-dexamethasone produced a clinically meaningful response without new safety findings in Chinese patients with previously treated MM. Trial registration: NCT03029234.