Background: FLT3 mutations, found in ≈30% of pts with AML, are associated with a poor prognosis. Midostaurin is a multikinase inhibitor that targets FLT3 and other kinases involved in AML pathogenesis. In the phase 3, randomized, placebo-controlled RATIFY trial, midostaurin + chemo significantly improved OS and EFS in adults (aged 18-59 y) with ND FLT3-mutated AML. The chemo regimen in RATIFY was 7+3 induction (1-2 cycles of cytarabine [Ara-C] 200 mg/m²/d on d1-7 + daunorubicin 60 mg/m²/d on d1-3) and consolidation (≤4 cycles of Ara-C 3000 mg/m²/d every 12 h on d1, 3, 5). Midostaurin + chemo was approved in the United States and Europe for pts aged ≥18 y with ND FLT3-mutated AML. However, many institutions use different chemo regimens as the standard of care (SOC). The aim of this new study is to assess the safety and efficacy of midostaurin 50 mg bid in combination with different SOC chemo regimens and as single-agent maintenance. Methods: CPKC412A2408 (NCT03379727) is an open-label, single-arm, multicenter, phase 3b study in adults aged ≥18 y and fit for chemo with ND AML per WHO 2008 classification, ECOG performance status of ≤2, and a documented FLT3 internal tandem duplication or tyrosine kinase domain mutation (estimated enrollment, 300). Pts must start their first induction chemo cycle with 7+3 (Ara-C 100-200 mg/m²/d on d1-7 + daunorubicin 60-90 mg/m²/d or idarubicin 12 mg/m²/d on d1-3) or 5+2 (a reduced-dose regimen with these agents) per investigator’s discretion and enroll by d7 of the first induction cycle. Once pts start on 7+3 or 5+2, they may not switch. Pts will receive consolidation with Ara-C, with dose per investigator’s choice. Midostaurin 50 mg bid will be administered on d8-28 of each 28-d induction and consolidation cycle and daily for ≤12 cycles of maintenance. Pts will discontinue the study if not in complete remission (CR) or CR with incomplete hematologic recovery (CRi) at the end of induction or consolidation or if they receive a stem cell transplant. The primary and secondary endpoints are safety and the proportion of pts achieving CR/CRi, respectively. Clinical trial information: NCT03379727