Foghorn Therapeutics Inc. announced the first patient has been dosed in the Phase 1 study of FHD-286 in combination with decitabine or cytarabine in relapsed and/or refractory acute myelogenous leukemia (AML). As previously reported, in the Phase 1 monotherapy dose escalation study, reductions in both peripheral and bone marrow blast counts, as well as recoveries in absolute neutrophil count (ANC), were observed in a subset of heavily pre-treated relapsed and/or refractory patients, irrespective of mutational status. Across a broad range of patients, differentiation was observed both morphologically and/or through biomarkers.

Additionally, patients with evaluable paired bone marrow biopsies demonstrated differentiation as measured by changes in CD11b+ cells, CD34+ cells, and other associated biomarkers. In addition, preclinical models with various combination agents including decitabine and cytarabine demonstrated improved survival benefit vs. the single-agent control arms. FHD-286 Phase 1 AML Combination Study Details: FHD-286 will be dose escalated in combination with either fixed-dose decitabine or fixed-dose cytarabine in a standard 3+3 dose escalation design.

The study will enroll relapsed and/or refractory AML patients. The study will assess the safety, tolerability, and efficacy of the combination regimens. To learn more about the Phase 1 combination study of FHD-286.

FHD-286 is a highly potent, selective, allosteric, and orally available, small-molecule, enzymatic inhibitor of BRG1 (SMARCA4) and BRM (SMARCA2), two highly similar proteins that are the ATPases, or the catalytic engines of the BAF complex, one of the key regulators within the chromatin regulatory system. In preclinical studies, FHD-286 has shown anti-tumor activity across a broad range of malignancies including both hematologic and solid tumors.