Published on June 4, 2021
Myelofibrosis Trial Kicks Off for Patients With Refractory Disease
Patients with refractory myelofibrosis may have a new treatment option on the horizon. The phase 3 IMpactMF trial has administered its first dose of GRN163L (Imetelstat) in a study that aims to show overall survival benefits with the novel agent versus the best available therapy (BAT).
“As the only study in refractory [myelofibrosis] with overall survival as the primary endpoint, dosing of the first patient in IMpactMF is an important step in developing [GRN163L] as a potential treatment for these patients,” Aleksandra Rizo, MD, PhD, said in a statement. Dr. Rizo is the chief medical officer at Geron Corporation, the biopharmaceutical company that manufactures the drug.
“With a median overall survival of only approximately 14 to 16 months for patients who fail or no longer respond to JAK inhibitor treatment, there is a significant unmet medical need for therapies that will improve survival,” Dr. Rizo added.
What is Imetelstat?
GRN163L is a first-in-class telomerase inhibitor. First-in-class means it uses a new and unique mechanism of action to treat this rare blood cancer. Telomerase inhibitor means it inhibits, or obstructs, telomerase, an enzyme that allows cancer cells to flourish by extending the protective caps (telomeres) at the ends of chromosomes. In preclinical studies, GRN163L shortened the protective caps, prompting the malignant cells to die.
The safety and tolerability of GRN163L were evaluated in phase 1 and phase 2 clinical trials. Adverse events included nausea, diarrhea, anemia, thrombocytopenia (low platelet levels), and neutropenia (low white blood cell levels).
Results from IMbark, the phase 2 study, were promising. GRN163L demonstrated multiple clinical benefits in the higher-dose arm of the trial, including improvement in overall survival and symptom response rates.
IMpactMF is a multicenter phase 3 clinical trial to evaluate GRN163L in patients with myelofibrosis who are refractory (non-responsive) to prior treatment with a JAK inhibitor. Approximately 320 patients are expected to enroll in the study, which launched on April 12, 2021, and is projected to end on May 1, 2024.
Participants will be randomly assigned to one of two study arms. Patients in the experimental arm will be treated with intravenous GRN163L at a dose of 9.4 mg/kg every 21 days until reaching one of four endpoints: disease progression, unacceptable toxicity, discontinuation of treatment, or study end.
Patients in the BAT arm will be treated with a non-JAK inhibitor, such as hydroxyurea, thalidomide (Thalomid), interferon, or chemotherapy, until reaching any of those same endpoints. Patients in the BAT arm who experience disease progression may be allowed to switch to GRN163L.
The primary endpoint of IMpactMF is overall survival. Secondary endpoints include symptom response, spleen response, progression-free survival, duration of response, safety, pharmacokinetics, and patient-reported outcomes.
Treatment Options for Refractory Myelofibrosis
The U.S. Food and Drug Administration (FDA) has approved two JAK inhibitors for treating myelofibrosis, with a potential third approval on the way. CTI BioPharma is seeking FDA approval of pacritinib to treat patients with myelofibrosis who have severe thrombocytopenia. However, patients who relapse after or are refractory to treatment with JAK inhibitors have no approved treatment options. Because of this unmet need, the FDA has granted Fast Track designation to GRN163L. This process helps expedite the development and review of new drugs to treat life-threatening conditions.
An interim analysis of IMpactMF is expected in 2024, with a full analysis in 2025. Patient Power will continue to update you as results are shared. For more information about GRN163L, contact an MPN specialist or visit Clinical Trials.gov.
See Our Sources
- Phase 3 Trial Information:
- Clinical Trials.Gov. (2021) “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.” https://clinicaltrials.gov/ct2/show/NCT04576156?term=imetelstat&draw=2&rank=3
- Geron. (2021) “Geron Announces First Patient Dosed in IMpactMF Phase 3 Clinical Trial in Refractory Myelofibrosis.” http://ir.geron.com/investors/press-releases/press-release-details/2021/Geron-Announces-First-Patient-Dosed-in-IMpactMF-Phase-3-Clinical-Trial-in-Refractory-Myelofibrosis/default.aspx
- Phase 2 Trial Information:
- Clinical Trials.Gov. (2020) “A Study to Evaluate Activity of 2 Dose Levels of Imetelstat in Participants With Intermediate-2 or High-Risk Myelofibrosis (MF) Previously Treated With Janus Kinase (JAK) Inhibitor.” https://clinicaltrials.gov/ct2/show/NCT02426086?term=imetelstat&draw=2&rank=2
- American Society of Hematology. (2020) “53 Favorable Overall Survival with Imetelstat Treatment Correlates with Other Clinical Benefits in Intermediate 2 or High Risk Myelofibrosis Relapsed/Refractory to Janus Kinase Inhibitor.” https://ash.confex.com/ash/2020/webprogram/Paper141013.html
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