Dr Watts on the Potential Advantages of INCB057643 in Advanced Myelofibrosis

"We think 1 advantage of the drug is that it can be given continuously… This may be the reason why we see such good symptom responses. We’ll [have to] see if we’re correct in terms of [labeling INCB057643] as best in class."

Justin M. Watts, MD, associate professor of medicine, Division of Hematology, chief, Leukemia Section, University of Miami Sylvester Comprehensive Cancer Center, discusses the potential advantages of the oral small molecule BET inhibitor INCB057643 vs other agents in this drug class in patients with advanced myelofibrosis and other advanced myeloproliferative neoplasms (MPNs).

Findings from an ongoing phase 1 dose-escalation/expansion study (NCT04279847) presented at the 2024 ASCO Annual Meeting highlighted the tolerability and clinical activity of INCB057643, a BET inhibitor, both as monotherapy and in combination with ruxolitinib (Jakafi). Across both arms, the treatment was generally well tolerated at doses of 4 mg to 10 mg, with no fatal treatment-related adverse effects (AEs) reported. Grade 3 or higher treatment-emergent AEs (TEAEs) were observed in 61.4% of patients, and 25.0% experienced serious TEAEs. Both treatment arms demonstrated improvements in spleen volume and symptom burden, suggesting clinical benefit.

One key advantage of INCB057643 is its ability to be administered continuously without planned dose holds, although dose adjustments or temporary holds can be made if AEs occur, Watts begins. Continuous exposure to the BET inhibitor appears critical for maintaining symptom responses, as interruption could lead to rebounds in MYC and cytokine levels, he notes. This sustained exposure may contribute to the consistent reduction in symptom burden observed, although the effect on spleen volume appears more stable over time, Watts explains.

These results reinforce the potential of INCB057643 as an active agent in this drug class, with ongoing evaluation needed to confirm whether it represents a best-in-class BET inhibitor, he says. The findings also underscore the promise of this approach for delivering meaningful benefits in patients with conditions characterized by elevated MYC and cytokine activity, Watts concludes.