Phase 1 study of Azacitidine in Combination with Quizartinib in patients with FLT3 or CBL mutated MDS and MDS/MPN

We conducted a phase 1 study evaluating 3 dose levels of quizartinib (30mg, 40mg or 60mg) in combination with azacitidine for HMA-naïve or relapsed/refractory MDS or MDS/MPN with FLT3 or CBL mutations. Overall, 12 patients (HMA naïve: n=9, HMA failure: n=3) were enrolled; 7 (58%) patients had FLT3 mutations and 5 (42%) had CBL mutations. The maximum tolerated dose was not reached. Most common grade 3-4 treatment-emergent adverse events were thrombocytopenia (n=5, 42%), anemia (n=4, 33%), lung infection (n=2, 17%), skin infection (n=2, 17%), hyponatremia (n=2, 17%) and sepsis (n=2, 17%). The overall response rate was 83% with median relapse-free and overall survivals of 15.1 months (95% CI 0.0-38.4 months) and 17.5 months (95% CI NC-NC), respectively. FLT3 mutation clearance was observed in 57% (n=4) patients. These data suggest quizartinib is safe and shows encouraging activity in FLT3-mutated MDS and MDS/MPN. This study is registered at Clinicaltrials.gov as NCT04493138.