Phase 1b study of unesbulin plus dacarbazine for the treatment of locally recurrent, unresectable of metastatic, relapsed or refractory leiomyosarcoma

A multicenter phase 1b study was designed to determine the recommended phase 2 dose (RP2D) and to evaluate the safety and preliminary efficacy of unesbulin (PTC596) in patients with advanced leiomyosarcoma (LMS). Adult patients with locally advanced, unresectable or metastatic, relapsed or refractory LMS were treated with escalating doses of unesbulin orally twice per week in combination with dacarbazine 1,000 mg/m² intravenously once every 21 days. The combination had promising efficacy. Unesbulin 300 mg was identified as the RP2D. At the RP2D, among subjects who were efficacy evaluable the objective response rate was 24.1%. The authors conclude that unesbuline 300 mg twice per week plus dacarbazine 1,000 mg/m² once every 21 days had a favorable benefit-risk profile in a heavily pretreated population of adults with advanced LMS.