Background: Selinexor is an oral, selective inhibitor of nuclear export that specifically blocks exportin 1, leading to the nuclear accumulation & reactivation of tumor suppressor proteins. Twice weekly (BIW) bortezomib in combination with dexamethasone (Vd) is an established therapy in relapsed and refractory multiple myeloma (RRMM). While the activity of bortezomib (bort) BIW in combination with other agents is efficacious, prolonged use is limited due to peripheral neuropathy (PN) (50-60%) as well as acquired resistance to bort. Preclinical studies have shown that selinexor, when combined with bort, can restore sensitivity of bort-resistant MM, inhibiting tumor growth and increasing survival in murine MM xenografts. In a Ph 1b/2 study, the combination of weekly selinexor with weekly bort and dex (SVd) was well tolerated and highly active with an ORR of 83% in patients (pts) with PI non-refractory MM, furthermore PN was limited to 14%. In addition, in pts with PI refractory MM, an ORR of 43% was observed, supporting selinexor can resensitize myeloma to PI based therapies. Methods: The BOSTON trial (NCT03110562) is a global Ph III study of selinexor in combination with weekly bort and dex (QW SVd) vs BIW bort in combination with dex (BIW Vd), in pts with RRMM who have received 1 to 3 prior anti-MM regimens. The QW regimen of SVd may provide for a higher ORR and improved duration of response as well as provide for a considerable reduction (~40%) in overall bort dose vs BIW Vd arm, which may be associated with better tolerability (e.g., PN) compared with second-line Vd-based regimens. After progressive disease is confirmed by an Independent Review Committee, pts in the Vd arm may crossover to SVd. Crossover to Sd is allowed as compassionate use for pts who are not able to tolerate continued treatment with bort. Progression Free Survival (PFS) and ORR are primary endpoints. Secondary endpoints include overall survival and duration of response. An ORR primary analysis is planned after the last pt randomized has had the opportunity to complete at least 2 MM evaluations. Clinical trial information: NCT03110562