Geron announces result from IMproveMF study at ASH

Geron (GERN) announced results from an oral presentation at the 66th American Society of Hematology, or ASH, annual meeting, reporting Phase 1 findings from the two-part IMproveMF study. The safety results from the dose escalation Part 1 suggest the tolerability of Rytelo, a telomerase inhibitor, in combination with ruxolitinib as frontline therapy in patients with intermediate-1, intermediate-2 or high-risk myelofibrosis. Based on the dose escalation findings in Part 1, imetelstat 9.4 mg/kg dosed every four weeks with ruxolitinib was the selected dose for the dose expansion Part 2 of the study, which is currently enrolling patients. IMproveMF is an ongoing, multicenter Phase 1/1b trial that aims to evaluate the safety, pharmacokinetics, and clinical activity of imetelstat in combination with ruxolitinib in patients with INT-1/INT-2/HR MF. As of the November 4, cutoff date, at least three patients had received each imetelstat dose level: Dose Level 1, imetelstat 4.7 mg/kg; Dose Level 2, imetelstat 6.0 mg/kg; Dose Level 3, imetelstat 7.5 mg/kg; and Dose Level 4, imetelstat 9.4 mg/kg. Ruxolitinib doses were individualized per patient. The PK profiles of imetelstat and ruxolitinib were consistent with previous monotherapy studies of imetelstat and ruxolitinib. At the time of this analysis, the median duration of imetelstat treatment for the seven patients in the imetelstat 9.4 mg/kg cohort was 12.1 weeks. The combination of imetelstat with ruxolitinib was well-tolerated, and no dose-limiting toxicities were reported at any imetelstat dose level within the first 28 days of Cycle 1. Grade 3 treatment-emergent adverse events were reported in 47% of patients, with anemia reported in 24%, neutropenia in 18%, leukopenia in 12%, and abdominal pain, fatigue, pneumonia and epistaxis each reported in 6% of patients. No Grade 4 or 5 TEAESs were reported. For patients in the 9.4 mg/kg imetelstat dose level selected for dose expansion in Part 2 of the study, hematology values, including hemoglobin, leukocytes, neutrophils and platelets, were stable over time. Across all four dose cohorts, average absolute change from baseline total symptom score over week 12 was a median of -5 and maximum absolute reduction from baseline TSS up to Week 24 was a median of -5. A trend for dose-dependent spleen volume reduction (SVR) at Week 24 was observed in the first three doses. Further evidence is needed in the 9.4 mg/mg dose where Week 24 data were not available at the time of this analysis. Preliminary results showed variant allele frequency (VAF) reductions in JAK2, CALR, MPL and high molecular risk driver mutations across the four dose cohorts. IMproveMF is actively enrolling patients for dose confirmation and expansion. In parallel, the separate IMpactMF Phase 3 trial is ongoing in MF patients who are relapsed/refractory to JAK inhibitors. This Phase 3 trial is designed to confirm the results from the IMbark Phase 2 study, where single-agent imetelstat treatment resulted in multiple clinically meaningful benefits, including symptom response and potential improvement in overall survival.