Results from phase 1 of the MANIFEST clinical trial to evaluate the safety and tolerability of pelabresib in patients with myeloid malignancies.

Pelabresib (CPI-0610), a BET protein inhibitor, is in clinical development for hematologic malignancies, given its ability to target NF-κB gene expression. The MANIFEST phase 1 study assessed pelabresib in patients with acute leukemia, high-risk myelodysplastic (MDS) syndrome, or MDS/myeloproliferative neoplasms (MDS/MPNs) (NCT02158858). Forty-four patients received pelabresib orally once daily (QD) at various doses (24-400 mg capsule or 225-275 mg tablet) on cycles of 14 d on and 7 d off. The most frequent drug-related adverse events were nausea, decreased appetite, and fatigue. The maximum tolerated dose (MTD) was 225 mg tablet QD. One patient with chronic myelomonocytic leukemia (CMML) showed partial remission. In total, 25.8% of acute myeloid leukemia (AML) patients and 38.5% of high-risk MDS patients had stable disease. One AML patient and one CMML patient showed peripheral hematologic response. The favorable safety profile supports the ongoing pivotal study of pelabresib in patients with myelofibrosis using the recommended phase 2 dose of 125 mg tablet QD.CLINICAL TRIAL REGISTRATION: NCT02158858.