Geron Halts Phase 3 Imetelstat Trial in Relapsed/Refractory Myelofibrosis

Geron Corporation has discontinued the phase 3 IMpactMF trial (NCT04576156) evaluating imetelstat (Rytelo) in patients with relapsed/refractory (R/R) myelofibrosis (MF) following a recommendation from an independent data monitoring committee (IDMC) that the study was unlikely to meet its primary end point of overall survival (OS).¹

The decision, announced October 28, 2026, followed the committee’s assessment that imetelstat was unlikely to demonstrate an OS benefit compared with best available therapy (BAT). Geron reported that no new safety signals were observed that would change imetelstat’s known safety profile or require additional safety monitoring. The company plans to conduct a detailed analysis of the trial data and share the findings with the scientific community at a future date.

“Given the recommendation from the [IDMC], we believe discontinuing our phase 3 IMpactMF trial at this time is the right course of action,” Joseph E. Eid, MD, executive vice president of research and development and chief medical officer of Geron, stated in the announcement.

IMpactMF Trial Design and Patient Population

The randomized, open-label, phase 3 IMpactMF trial enrolled 327 patients with intermediate-2 or high-risk MF whose disease had relapsed or was refractory following treatment with a Janus kinase (JAK) inhibitor.¹

The study was designed to evaluate whether imetelstat could improve OS compared with BAT, addressing an unmet need for patients whose disease progresses after JAK inhibitor therapy. Participants were randomly assigned in a 2:1 ratio to receive intravenous imetelstat at 9.4 mg/kg every 3 weeks or BAT.¹

Eligible patients included adults with primary MF, post–essential thrombocythemia MF, or post–polycythemia vera MF. Participants were required to have measurable splenomegaly and active disease-related symptoms. Patients were also ineligible for allogeneic stem cell transplantation.²

OS served as the primary end point, with secondary outcomes including symptom response, progression-free survival, spleen response, complete remission, changes in bone marrow fibrosis, and safety.²

Implications for Imetelstat Development

Imetelstat is a telomerase inhibitor approved for certain adults with lower-risk myelodysplastic syndrome (MDS). Its mechanism of action distinguishes it from JAK inhibitors, which are commonly used to manage MF-related symptoms and splenomegaly.¹

The IMpactMF discontinuation represents a setback for evaluating imetelstat in the post-JAK inhibitor MF setting. However, the company has not yet released a detailed analysis of the trial data, and the announcement does not provide comparative efficacy results or quantify the observed OS difference.

Geron stated that it remains committed to analyzing the findings to identify potential insights for future research while continuing to develop its commercial business in low-risk MDS.¹

The findings from IMpactMF may help clarify the role of telomerase inhibition in MF, although additional data will be needed to understand the reasons behind the trial’s projected failure to meet its primary end point.

REFERENCES

1. Geron Corporation provides update on phase 3 IMpactMF clinical trial of imetelstat in relapsed/refractory myelofibrosis. News release. Geron Corporation. October 28, 2026. Accessed October 29, 2026. https://tinyurl.com/jcs59cru 

2. A study of imetelstat in participants with myelofibrosis who are relapsed or refractory to Janus kinase inhibitor treatment (IMpactMF). ClinicalTrials.gov. Updated December 4, 2025. Accessed October 29, 2026. https://clinicaltrials.gov/study/NCT04576156