*1.6.1 Uproleselan*

Uproleselan (GMI-1271) is a novel antagonist of E-selectin that down-regulates cell survival pathways and enhances chemotherapy response. In a single arm phase I/II trial of 47 adults with relapsed/refractory AML were treated with GMI-1271 in combination with MEC chemotherapy. GMI-1271 was given 24 hrs prior, then every 12 hrs during and for 48 hrs post induction/consolidation. With a median follow-up of 11 months, the ph 1 median leukemia free survival was not reached and overall survival was 7.6 months. ORR (CR/CRi/MLFS/PR) was evaluable in 21 patients was 50%. Remission rate (CR/CRi) was 45%.Common Gr 3/4 AEs were febrile neutropenia, sepsis, bacteremia, hypoxia. 30 and 60 day mortality were 0 and 7%, respectively [101]. A pivotal phase 2/3 study (NCT03616470) is underway to assess the efficacy and safety of uproleselan with standard salvage chemotherapy in R/R AML. The study is a global, randomized, double-blind, phase 3 trial in adults aged 18–75 years with R/R AML and fit for chemotherapy [102].
