Study Will Analyze Imetelstat-Jakafi Combination for Myelofibrosis

The first patient has been treated in the phase 1 IMproveMF clinical trial evaluating frontline imetelstat plus Jakafi (ruxolitinib) in patients with myelofibrosis, a rare type of blood cancer, according to Geron, the drug company manufacturing imetelstat.

The design for the trial is based off preclinical data that showed that treatment with Jakafi then imetelstat inhibited myelofibrosis cells, while sparing healthy cells.

“Given these preclinical data, we want to explore the potential for disease modification with imetelstat in the earlier, frontline disease setting,” Dr. Faye Feller, executive vice president and chief medical officer of Geron, said in a press release.

IMproveMF is a two-part study that will analyze the safety of imetelstat plus Jakafi, as well as how the drug duo moves throughout the body (pharmacokinetics) and effects (pharmacodynamics) of the drug combination in patients with intermediate-2 or high-risk myelofibrosis.

While Jakafi can help with the symptoms of myelofibrosis, it does not actually improve the disease itself. One of the study’s authors noted that the hope is that the addition of imetelstat to Jakafi will improve patient outcomes.

“Upon diagnosis, intermediate-2 and high-risk myelofibrosis patients typically receive (Jakafi) as the primary therapy, which reduces enlarged spleens and alleviates symptoms, but does not change the course of the disease,” lead study author Dr. John Mascarenhas, a professor of medicine at the Icahn School of Medicine at Mount Sinai in New York City, said in the release.

“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 (Jakafi),” Mascarenhas added.

The first part of the study will include approximately 20 patients with myelofibrosis who have received Jakafi. Then, they will receive imetelstat at increasing doses, based on safety and tolerability. The goal of part 1 is to identify a safe dose of imetelstat to give alongside Jakafi.

Part 2 of the trial will include patients who have not had prior treatment with Jakafi or another JAK inhibitor. They will receive single-agent Jakafi for 12 or more weeks before the addition of imetelstat. Researchers will then analyze the preliminary clinical activity of the drug combination.

Eligible patients can enroll in the trial, which will take place at the University of Miami (currently recruiting), H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida (not yet recruiting), and the Icahn School of Medicine at Mount Sinai.

Geron said that preliminary results are expected by the end of 2023.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.