On August 22, 2022 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, reported that the first patient has been dosed in IMproveMF, a Phase 1 study evaluating imetelstat, a first-in-class telomerase inhibitor, in combination with ruxolitinib in patients with frontline myelofibrosis (MF) (Press release, Geron, AUG 22, 2022, View Source [SID1234618540]).
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"We designed the Phase 1 IMproveMF study based on preclinical data that showed the sequential treatment of ruxolitinib followed by imetelstat had a selective inhibitory effect on malignant MF stem cells, while sparing normal hematopoietic stem cells. This disease-modifying potential of imetelstat to affect the malignant clones driving disease progression differentiates it from any other drug currently approved or in development for myelofibrosis treatment," said Faye Feller, MD, Executive Vice President, Chief Medical Officer of Geron. "Given these preclinical data, we want to explore the potential for disease modification with imetelstat in the earlier, frontline disease setting. In parallel, our 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."
"Upon diagnosis, intermediate-2 and high-risk myelofibrosis patients typically receive ruxolitinib as the primary therapy, which reduces enlarged spleens and alleviates symptoms, but does not change the course of the disease. As a non-JAK inhibitor treatment option with a potentially novel mechanism of action, imetelstat could provide an additive benefit of disease modification when combined with ruxolitinib," said John Mascarenhas, MD, Professor of Medicine at the Icahn School of Medicine at Mount Sinai and a principal investigator on the IMproveMF study. "The dosing of the first patient is an important step in identifying a potential safe and efficacious dose and schedule of imetelstat and ruxolitinib in frontline MF."
IMproveMF is a single arm, open label, two-part Phase 1 study to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of imetelstat in combination with ruxolitinib as a frontline treatment in patients with Intermediate-2 or High-risk MF (frontline MF). In both parts, patients will receive ruxolitinib followed by imetelstat, a dosing schedule that showed synergistic and additive effects of the two drugs in preclinical experiments. Part 1 will enroll up to 20 frontline MF patients who, at the time of enrollment, have received an optimized dose of ruxolitinib, to which imetelstat treatment will be added at increasing dose levels based on safety and tolerability. The primary purpose of Part 1 is to identify a safe dose for treating frontline MF patients with a combination of imetelstat and ruxolitinib. If a safe dose is identified in Part 1, participants in Part 2 will be JAK inhibitor naïve and will receive treatment with ruxolitinib after screening and enrollment at a starting dose based on standard-of-care or local prescribing information. Treatment with single-agent ruxolitinib will continue for at least 12 weeks, including four consecutive weeks at a stable dose prior to the addition of imetelstat. Part 2 is designed to confirm the safety profile of imetelstat in combination with ruxolitinib and to evaluate for preliminary clinical activity of the combination. Geron expects to present preliminary results from this study by the end of 2023.
The study is enrolling patients and is being conducted at three trial sites in the U.S., two of which are currently open for patient screening. For more information, please visit ClinicalTrials.gov (Identifier NCT05371964).
About Imetelstat
Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic malignancies. Data from Phase 2 clinical trials provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity. Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis stimulating agent and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment.