Updated IMproveMF Protocol Advances Imetelstat Plus Ruxolitinib Into Phase 1b in Frontline Myelofibrosis
Results from an updated protocol presented at the American Society of Clinical Oncology (ASCO) Annual Meeting describe the phase 1b expansion of the IMproveMF trial, which is evaluating imetelstat plus ruxolitinib as frontline therapy for patients with intermediate- or high-risk myelofibrosis.
“In preclinical evaluations, sequential treatment with [ruxolitinib], a Janus kinase inhibitor, and [imetelstat], a telomerase inhibitor, selectively reduced [myelofibrosis] hematopoietic stem cells and progenitor cells,” stated John Mascarenhas, MD, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York. “These findings, and the nonoverlapping mechanisms of action, supported the evaluation of [imetelstat plus ruxolitinib] in frontline [myelofibrosis].”
The protocol update follows completion of the phase 1 dose-escalation portion of the study, which established the recommended phase 1b dose of imetelstat. Investigators reported that the combination was generally well tolerated across all evaluated dose levels, with no dose-limiting toxicities observed. Preliminary findings also demonstrated dose-dependent clinical activity, while pharmacokinetic analyses were consistent with those reported for each agent as monotherapy. Based on these results, 8.9 mg/kg of imetelstat administered intravenously every 4 weeks was selected for continued evaluation in phase 1b.
The phase 1b portion of IMproveMF will enroll adults with intermediate-1-, intermediate-2-, or high-risk myelofibrosis, an Eastern Cooperative Oncology Group performance status of 2 or less, and no prior history of hematopoietic stem cell transplantation. Following a protocol amendment implemented in November 2025, enrollment has been limited to patients already receiving first-line ruxolitinib for at least 12 weeks who have remained on a stable dose for a minimum of 4 weeks before initiating imetelstat. Patients previously enrolled in cohort A will continue treatment according to protocol, while all new enrollment will occur in cohort B.
The primary objectives of phase 1b are to evaluate safety and symptom improvement at week 24, defined as the proportion of patients achieving at least a 50% reduction in total symptom score after combination treatment. Secondary end points include changes in symptom burden, spleen response, and progression-free survival.
Enrollment into cohort B is ongoing. The primary analysis is planned approximately 6 months after the final enrolled patient receives the first dose of imetelstat plus ruxolitinib.
Source:
Mascarenhas J, Kuykendall AT, Bradley TJ, et al. Updated protocol: IMPROVEMF, a phase 1b trial of imetelstat (IME)+ ruxolitinib (RUX) in patients (pts) with intermediate (INT)-1/2 or high-risk (HR) myelofibrosis (MF). Presented at the 2025 ASCO Annual Meeting; May 30–June 3, 2025; Chicago, Illinois. Abstract TPS6604.
