Investigators Discontinue Phase 3 Trial of Imetelstat in R/R Myelofibrosis

Geron Corporation will discontinue the phase 3 IMpactMF trial (NCT04576156) evaluating imetelstat (Rytelo) in patients with relapsed/refractory myelofibrosis following prior treatment with a JAK inhibitor, according to a press release from the developers.¹ The decision was based on a recommendation from the trial’s independent data monitoring committee (DMC), which advised that the study was unlikely to meet its primary end point of overall survival (OS).

Why was the trial discontinued?

The independent DMC advised developers that IMpactMF was unlikely to meet its primary end point of OS, prompting the decision to discontinue the trial. According to the company, there were no new safety signals observed that change the known safety profile of imetelstat or require additional safety monitoring. Developers stated that a detailed analysis of the data will be conducted and that study findings will be shared with the scientific community at a future date.

"Given the recommendation from the DMC, we believe discontinuing our phase 3 IMpactMF trial at this time is the right course of action. We are deeply grateful to the patients and families, as well as the investigators and clinical teams whose dedication made this research possible," said Joseph E. Eid, MD, executive vice president of research and development and chief medical officer of Geron, in a news release.¹ "Hematologic malignancies are complex diseases, with distinct biological characteristics and treatment challenges across patient populations. We remain committed to thoroughly evaluating the data, understanding what we can learn, and sharing insights that may help inform future research and address the significant unmet needs that remain."

What was the IMpactMF trial design?

IMpactMF was an open-label, controlled phase 3 trial that evaluated 327 patients with intermediate-2 or high-risk myelofibrosis who were relapsed or refractory to a JAK inhibitor. Patients were randomly assigned 2:1 to receive imetelstat or best available therapy, with the trial designed to evaluate a potential improvement in OS with imetelstat. Patients in the imetelstat arm received the telomerase inhibitor at 9.4 mg/kg intravenously every 3 weeks.

The trial’s secondary end points included symptom response rate, progression-free survival, spleen response rate, reduction in the degree of bone marrow fibrosis, and pharmacokinetics.² The investigators also intended to evaluate health-related quality of life based on European Organization for Research and Treatment of Cancer Quality-of-Life-Questionnaire-Core-30 (EORTC QLQ-C30) scores.

Patients 18 years and older with measurable splenomegaly demonstrated by a palpable spleen measuring at least 5 cm below the left costal margin or a spleen volume at least 450 cm³ by MRI or CT, acceptable hematology laboratory test values, and an ECOG performance status of 0 to 2 were eligible for enrollment on the trial. Those with major surgery within 28 days of randomization or active systemic hepatitis infection requiring treatment were ineligible for study entry.

What are the implications for imetelstat?

Imetelstat is a telomerase inhibitor approved in the US and the European Union for certain patients with lower-risk myelodysplastic syndromes (LR-MDS). The discontinuation applies to the agent’s investigational use in myelofibrosis and does not affect its approved indication. Developers indicated that they will continue to analyze the IMpactMF data while focusing on their commercial LR-MDS business. "As we fully analyze the data from the IMpactMF trial, we remain committed to growing Rytelo demand in the US and broadening access to eligible [patients with] LR-MDS outside the US," said Harout Semerjian, president and chief executive officer of Geron, in the news release.¹

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 28, 2026. https://tinyurl.com/db6mr4k5
2. A study comparing imetelstat versus best available therapy for the treatment of intermediate-2 or high-risk myelofibrosis (MF) who have not responded to Janus kinase (JAK)-inhibitor treatment (IMpactMF). ClinicalTrials.gov. Updated July 8, 2026. Accessed October 28, 2026. https://tinyurl.com/rv4m82ay