BET Inhibitor Appears Safe and Well-Tolerated in Patients With Relapsed or Refractory Myelofibrosis

Treatment using the bromodomain and extra-terminal (BET) inhibitor INCB057643 as a monotherapy and in combination with ruxolitinib appears well-tolerated in patients with advanced hematologic malignancies, specifically relapsed or refractory myelofibrosis (R/R MF), according to a study presented at the 2023 ASCO® Annual Meeting in Chicago, Illinois.

In this ongoing, phase 1, 3+3 dose-escalation/expansion study, INCB057643 monotherapy therapy has been assessed for safety and tolerability in 13 patients with R/R MF, myelodysplastic syndromes (MDS), or MDS/myeloproliferative neoplasm (MPN) overlap syndromes (MDS/MPN) or added to ruxolitinib in patients with MF and suboptimal response to ruxolitinib. The primary end point of interest was defined as safety and tolerability, including identification of dose-limiting toxicities (DLTs).

According to the results, thrombocytopenia was the most common treatment-emergent adverse event (TEAE; n=9) and the only TEAE leading to discontinuation (n=3).

“Treatment with INCB057643 monotherapy (4 and 8 mg qd) and in combination (4 mg qd) with [ruxolitinib] was generally well-tolerated in this [patient] population,” the researchers concluded. They added that “the 12-mg qd monotherapy dose was not tolerated and caused 2 DLTs. There were no treatment-related fatal events. Dose finding in part 1 is ongoing with 10 mg qd, after which a recommended phase 2 dose will be declared. Combination dose escalation is also ongoing.”