A Phase 1b/2 Study of Navtemadlin (KRT-232), a Murine Double Minute 2 Inhibitor, Combined with a BCR-ABL Tyrosine Kinase Inhibitor in Patients with Relapsed/Refractory, TP53WT, Ph+ Chronic Myeloid Leukemia

Background: BCR-ABL tyrosine kinase inhibitors (TKI) can provide symptom control and improve survival in patients with Ph+ chronic myeloid leukemia (CML), however, elimination of leukemic stem cells (LSC) remains a significant unmet medical need. Persisting LSCs contribute to resistance and disease relapse, which can occur in approximately 50% of patients who elect to discontinue TKIs after sustained deep molecular responses (Cortes et al. Am J Hematol. 2018). Furthermore, patients in accelerated or blast phase have lower response rates, shorter response duration, and inferior survival outcomes. Patients who are not eligible for stem cell transplant or other TKIs after failure of at least 2 prior TKIs are especially in need of effective treatment options.