John Mascarenhas, MD, Icahn School of Medicine at Mount Sinai, New York, NY, discusses a Phase Ib/II study (NCT04485260) aiming to evaluate the efficacy of KRT-232, a novel MDM2 inhibitor, in myelofibrosis patients. By inhibiting MDM2, KRT-232 is intended to restore wild-type p53 activity, thus inducing apoptosis in the stem and progenitor cell populations of the malignancy. MDM2 inhibitors are an exciting approach for myelofibrosis patients with poor prognosis, who have failed ruxolitinib and are in need of second-line therapy. KRT-232 and ruxolitinib combination therapy is being evaluated in advanced myelofibrosis as well as post–polycythemia vera myelofibrosis. Clinical activity of the drug was observed, with patients exhibiting splenic symptom responses. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.