FDA lifts clinical hold on phase I study of FHD-286 in patients with R/R AML or MDS

On June 1, 2023, the U.S. Food and Drug Administration (FDA) lifted the clinical hold on the phase I dose escalation study of FHD-286, a highly potent, selective, allosteric, orally available inhibitor of BRG1 (SMARCA4) and BRM (SMARCA2) for the treatment of patients with relapsed and/or refractory (R/R) acute myeloid leukemia (AML) (NCT04891757).¹

Following initiation of a partial clinical hold on May 19, 2022,² the FDA then placed a full clinical hold on the phase I study on August 23, 2022, due to suspected cases of fatal differentiation syndrome.³ In response to the clinical hold, an independent adjudication committee of leading AML experts determined that the rate of differentiation syndrome was 15%, with one case considered definitive for differentiation syndrome but not contributing to the patient’s death.¹

The clinical hold has been lifted following protocol amendments and plans to initiate a phase I study of FHD-286 in combination with decitabine or low-dose cytarabine in patients with R/R AML.¹ Decitabine and cytarabine are cytoreductive and may reduce the risk of differentiation syndrome.  This phase I combination study, to assess the safety, tolerability, and efficacy of FHD-286 in R/R AML, is expected to begin later in 2023; patients will receive a dose escalation of FHD-286 with fixed-dose decitabine or fixed-dose cytarabine in a 3+3 dose escalation design.¹