A phase I dose-escalation trial evaluating the safety of ruxolitinib plus abemaciclib is now enrolling certain patients who have primary or secondary myelofibrosis.
The trial will enroll patients with intermediate-1, intermediate-2, or high-risk disease who require treatment and had an “inadequate response” to ruxolitinib, according to a presentation by Jan Bewersdorf, MD, of the Memorial Sloan Kettering Cancer Center at the 2023 American Society of Clinical Oncology Annual Meeting.
Dr. Bewersdorf and colleagues defined an “inadequate response” to ruxolitinib as having palpable splenomegaly ≥5 cm below the left costal margin at study entry, having active myeloproliferative neoplasm (MPN) symptoms, or both. They defined active MPN symptoms as the presence of one symptom score of at least five or two symptom scores of at least three on the MPN Symptom Assessment Form Total Symptom Score.
The trial will follow a 3+3 dose-escalation design. Patients will receive increasing doses of abemaciclib and stable doses of ruxolitinib 10 mg or 15 mg twice daily.
The study’s primary endpoint is to determine the maximum tolerated dose of ruxolitinib plus abemaciclib. Its secondary endpoints include measures of efficacy.
“Exploratory endpoints include changes in allele fraction of driver mutations, gene expression profiling, and clonal architecture to identify biomarkers of response, mechanisms of resistance, and to assess for any disease-modifying effects of the combination therapy,” according to Dr. Bewersdorf and colleagues.
Dr. Bewersdorf and colleagues are conducting the study to address the need for “novel mechanism-based therapies” for patients who experience disease progression on ruxolitinib. The researchers previously showed that combining CDK4/6 inhibitors with ruxolitinib showed “synergistic effects in murine models” of myelofibrosis, “providing the preclinical rationale for this trial,” they wrote.
This trial is open for enrollment at Memorial Sloan Kettering Cancer Center and MD Anderson Cancer Center.
Bewersdorf JP, Verstovsek S, Derkach A, et al. Phase I study of ruxolitinib in combination with abemaciclib for patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. Abstract #TPS7086. Presented at the 2023 American Society of Clinical Oncology Annual Meeting; June 2-6, 2023; Chicago, Illinois.