ASH 2024 | Encouraging results of the BOREAS trial investigating navtemadlin in R/R myelofibrosis

So the BOREAS trial is a really exciting trial. It is the first randomized Phase III study of a therapy salvaging patients who were JAK inhibitor relapsed refractory MF, with a drug called navtemadlin, which is an MDM2 inhibitor, likely best in class, very active agent, has already shown very strong early clinical trial data, and now confirming it in the Phase III study of BOREAS, which is randomizing patients who are wild type P53 to either navtemadlin, 240 milligrams, seven days on, 21 days off, or best available therapy, excluding a JAK inhibitor, with a primary endpoint of SVR 35%, which was met in 15% of patients in the combination arm versus about 5% in patients who received BAT, which was interferon, lenalidomide, and other agents, hydroxyurea. 

So this really confirms, I think, what we’ve seen previously, but in a very large randomized study, significant clinical activity in terms of spleen reduction, but also symptom reduction. And then we have an abstract looking at the correlative data showing very potent reduction in circulating CD34 cells, driver mutation VAF, bone marrow fibrosis, and inflammatory cytokines, all of which also correlate with spleen volume reduction as a clinical outcome. So really tying in nicely biomarkers of disease modification with clinical outcome measures that are regulatory endpoints like SVR35. So very exciting study because really the first time we’re using a non-JAK inhibitor therapy in the relapsed/refractory setting demonstrating very significant clinical activity.

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