Vanflyta (quizartinib)

These results suggest that concomitant use of quizartinib and moderate CYP3A inducers should be avoided. Concomitant use of weak CYP3A inducers does not warrant dose adjustment, since the impact on quizartinib exposure is clinically nonrelevant.

P1/2, N=52, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

Among the screened compounds, apigenin, chrysin, and sakuranetin showed the highest binding affinities toward FLT3, with docking scores of - 10.1, - 9.8, and - 9.9 kcal/mol, respectively, compared with - 8.7 kcal/mol for Quizartinib...ELF and molecular electrostatic potential (MEP) analyses were performed to characterize charge distribution and interaction regions. All computational tools and parameters are described in the main manuscript.

Here we detail two patient cases illustrating the real-world use of quizartinib in combination with anthracycline and cytarabine-based chemotherapy and maintenance monotherapy for the management of FLT3-ITD+ AML. These cases highlight the practical recommendations on management of quizartinib-based chemotherapy in accordance with the Food and Drug Administration (FDA)-mandated REMS requirements. Adopting these strategies to optimize the safe treatment of FLT3-ITD+ AML with quizartinib may ultimately improve patient outcomes in this highly challenging malignancy.

In vivo, FYJ-195 induced profound tumor regression (TGI = 125%) in the MV4-11 xenograft model (10 mg/kg) and achieved robust tumor growth suppression (TGI = 68.6%) in the Ba/F3-FLT3-ITD-F691L model (50 mg/kg), where quizartinib was ineffective. Mechanistic studies confirmed that FYJ-195 effectively blocked FLT3 signaling and induced apoptosis without observable toxicity. Collectively, FYJ-195 represents a promising lead candidate for drug-resistant AML.

In patients with newly diagnosed FLT3-ITD-negative AML achieving CRc1, quizartinib improved OS and DFS in the overall population. Notably, the clinical benefit of quizartinib was observed regardless of allo-HCT, and appeared more evident in patients who did not proceed to transplant.

P1/2, N=113, Completed, PETHEMA Foundation | Recruiting --> Completed | N=84 --> 113 | Trial completion date: Nov 2024 --> May 2025

These subnetworks included hub genes such as IFIT1, PSMB9, and HLA-B, which are known to be associated with immune evasion and drug resistance in acute myeloid leukemia. Our findings demonstrate that the proposed method enables statistically reliable and biologically interpretable identification of phenotype-specific gene regulatory mechanisms, providing insights into potential therapeutic targets.

P2/3, N=350, Recruiting, Fundacion PETHEMA | Not yet recruiting --> Recruiting

P1/2, N=30, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=58 --> 30

In a Ba/F3 FLT3-ITD-F691L mouse model, nintedanib demonstrated superior anti-leukemic efficacy compared with gilteritinib and quizartinib. Furthermore, nintedanib potently inhibited primary AML blasts harboring FLT3-ITD while normal bone marrow remained intact. These findings identify nintedanib as a promising FLT3 inhibitor and support its further therapeutic investigation in FLT3-ITD-positive AML.

Functionally, MV4-11QR cells showed broad cross-resistance to clinically relevant agents, including midostaurin, venetoclax, and cytarabine. Importantly, pharmacological targeting of mutant p53 with eprenetapopt or MAPK signaling with trametinib restored sensitivity to quizartinib, inducing synergistic or additive cytotoxic effects and increased apoptosis. Together, these findings define a multilayered resistance program involving genetic, signaling, and metabolic adaptations and support rational combination strategies to overcome FLT3 inhibitor resistance in AML.