MEI Pharma reports clinical data on oral CDK9 inhibitor voruciclib at ASH 2023

MEI Pharma announced clinical data from the monotherapy dose escalation stage of the ongoing Phase 1 study evaluating voruciclib, a selective oral cyclin-dependent kinase 9 inhibitor, alone and in combination with venetoclax, a B-cell lymphoma 2 inhibitor, in patients with acute myeloid leukemia or B-cell malignancies, is highlighted in a poster session at the 65th American Society of Hematology Annual Meeting and Exposition. The Phase 1 study is a two stage, open-label, 3+3 dose escalation and expansion study evaluating voruciclib, a CDK9 inhibitor, as a monotherapy and in combination with venetoclax , a BCL2 inhibitor. The first stage of the study, evaluating the dose and schedule of voruciclib as a single-agent in patients with relapsed and refractory acute myeloid leukemia or B-cell malignances after failure of standard therapies, is complete. The second stage of the study is ongoing and is evaluating voruciclib in combination with venetoclax in patients with R/R AML. A total of 40 patients, median age 75 years, were enrolled in the first stage of the study evaluating voruciclib as a monotherapy. The majority of patients had AML and the remaining patients had B-cell malignancies. Enrolled patients were generally heavily pretreated; the median number of prior therapies was 3 and 5 patients had prior hematopoietic stem cell transplant. Patients enrolled in Cohort 1 of the monotherapy stage of the study were administered voruciclib once daily continuously at doses of 50 mg and 100 mg. Patients enrolled in Cohort 2 were administered voruciclib on an intermittent schedule on days 1-14 in a 28-day cycle implemented after 2 dose limiting toxicities were observed at 100 mg daily continuously. Dose escalation in Cohort 2 was stopped at 200 mg before reaching the maximum tolerated dose at this schedule to focus on evaluation of venetoclax in combination with voruciclib. The primary objectives of the study are to determine the safety and biologic effective dose of voruciclib monotherapy or voruciclib in combination with venetoclax. Secondary objectives of the study include assessing the preliminary efficacy, pharmacokinetics, pharmacodynamics, and biomarkers of voruciclib monotherapy or voruciclib in combination with venetoclax. In the 21 patients enrolled with AML, 1 patient at 100 mg achieved a morphologic leukemia-free state and 9 patients had disease stabilization, which lasted at least 3 months in 2 patients. In the 19 patients enrolled with B-cell malignancies, 4 patients had stable disease with a decrease in tumor size.