Quizartinib with Decitabine and Venetoclax

Overall, 28 pts were enrolled and evaluable at the time of this report. Of the 23 pts with R/R AML (median 3 [range 1-5] prior therapies, 78% with ≥1 prior FLT3i including prior gilteritinib (GILT) in 70%, and 39% had a prior ASCT), 78% achieved CRc (3 CR, 15 CRi) with 6/16 and 5/18 responders FLT3-PCR and multicolor flow cytometry (MFC) negative, respectively. Pts with RAS/MAPK mutations had the lowest response rates (Table). Interestingly, no emergent TKD mutations were noted at relapse after the triplet but 3/8 evaluable pts had emergent RAS/MAPK mutations. 60-day mortality rate was 5%. Of 5 patients with newly diagnosed AML (median age 69), all achieved CRc (2 CR, 3 CRi) with 4/5 and 2/4 responders FLT3-PCR and MFC negative, respectively. 60-day mortality was 0. 2 pts developed hematologic DLT with 40 mg/day QUIZ dose (grade 4 neutropenia with a <5% cellular BM lasting ≥42 days). Hence, QUIZ 30 mg/day dose was determined as RP2D for the triplet. Grade 3/4 non-hematologic toxicities included lung infections (42%) and neutropenic fever (30%). No QTcF prolongations >480 msec were noted. With a median follow-up (f/u) of 13 months, the median OS was 7.6 months in R/R cohort (1-year OS of 30%). 8/18 responding R/R pts (including 5/8 prior GILT exposed pts) underwent ASCT with a median OS of 19 vs 8 months in those who underwent ASCT versus not (p=0.26). Of the 5 frontline responding pts median OS was 14.5 months, 2 were alive in CR, 1 died in CR1 post-ASCT, 2 died due to relapsed disease at the last f/u. Conclusions: DAC + VEN + QUIZ is active in R/R FLT3-ITD mutated AML pts, with CRc rates of 78% and the median OS of 7.6 months. Interestingly, RAS/MAPK mutations but not emergent TKD mutations were associated with primary and secondary resistance to the triplet. Accrual continues, and updated clinical, NGS, and mass cytometry (CyTOF) data will be presented.