Study Works to Establish Dose and Safety of BET Inhibitor INCB057643 in Advanced Myeloid Neoplasms

An ongoing study is seeking to evaluate the safety, tolerability, and dose of INCB057643 with or without ruxolitinib in patients with relapsed or refractory myelofibrosis (MF) and other advanced myeloid neoplasms.

Early results indicate that treatment with INCB057643 as monotherapy was generally well tolerated at the 4 mg and 8 mg daily doses, as well as the 4 mg dose when combined with ruxolitinib. Dose escalation to 12 mg was not tolerated by the study sample. The results were presented at the 2023 American Society of Clinical Oncology Annual Meeting.

“Bromodomain and extra-terminal (BET) proteins are epigenetic readers that regulate expression of critical oncoproteins involved in the pathophysiology of hematologic malignancies, including myelofibrosis. INCB057643 is a small-molecule BET inhibitor,” explained the authors, led by Justin Watts, MD, of the Sylvester Cancer Center, University of Miami, in Florida.

Thus far, the researchers have enrolled 16 adult patients with MF (n=12) or MDS/MPN (N=4). They received the following treatments:

• 4 mg monotherapy (n=6)
• 8 mg monotherapy (n=4)
• 10 mg monotherapy (n=1)
• 12 mg monotherapy (n=2)
• 4 mg + ruxolitinib (n=3)

Nine patients have remained on treatment. Thrombocytopenia was the most common adverse event related to treatment and the only treatment-related reason for discontinuation (n=3). Three additional patients discontinued treatment due to progressive disease. Other grade 3 adverse events that led to treatment anemia (n=3) and hypokalemia (n=2). There were no treatment-related deaths.

The authors concluded that treatment with INCB057643 monotherapy was generally well tolerated at the 4 mg and 8 mg daily doses and at 4 mg in combination with ruxolitinib. However, the 12-mg dose was not tolerated. The researchers continue to investigate the 10 mg dose.

Reference

Watts JM, Hunter A, Iurlo A, et al. Bromodomain and extra-terminal (BET) inhibitor INCB057643 (LIMBER-103) in patients (pts) with relapsed or refractory myelofibrosis (R/R MF) and other advanced myeloid neoplasms: A phase 1 study. Abstract #7069. Presented at the 2023 American Society of Clinical Oncology Annual Meeting; June 2-6, 2023; Chicago, Illinois.