Background: Sor is a small molecule tyrosine kinase inhibitor that has many targets and previously was developed for the treatment of MM. Bor is a proteasome inhibitor widely used to treat multiple myeloma and other malignancies. In preclinical studies, the combination of Sor and Bor has been shown to modulate expression of BCL-family members and augment cytotoxicity in MM cell lines. Methods: Pts with MM were enrolled in cohorts of 3 during dose escalation to determine the maximum tolerated dose (MTD) of Sor twice daily (BID) in combination with Bor given days 1, 8, 15 of a 28 day cycle. The MTD was defined as the highest dose level at which less than 33% of pts exhibited a dose limiting toxicity (DLT). Efficacy, as measured by 6-month progression free survival (PFS) and response rate (RR) per RECIST, was documented. Results: Eleven pts were enrolled in 3 dose levels. DLTs (fatigue and rash respectively) were seen in 2 of 3 patients enrolled at the highest dose level (Sor 400 mg and Bor 1.3 mg/m²). The next lowest dose level (Sor 400 BID and Bor 1.0) enrolled 5 pts and none had DLTs. Thus, this dose level was defined as the MTD. Toxicities seen in >20% of pts included hypertension, pruritus, hand-foot syndrome, mucositis, nausea, vomiting, rash, constipation, abdominal pain, anorexia and fatigue. Of 9 response evaluable pts, none had radiographic evidence of tumor response. Two of 11 (18%) pts remained progression free for greater than 6 months. Conclusions: The combination of Sor and Bor is safe, but minimally active in pts with MM. In the absence of tumor response at or above the MTD, the study was closed with only 5 pts treated at the provisional MTD and enrollment to a planned dose expansion cohort will not occur. Clinical trial information: NCT01078961.