P2, N=25, Completed, H. Lee Moffitt Cancer Center and Research Institute | Active, not recruiting --> Completed

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.

P2/3, N=207, Active, not recruiting, Sobi Inc. | Recruiting --> Active, not recruiting

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

Moreover, FTY720 co-treatment resensitized G12D NRAS-mutated M14(R)701 cells to gilteritinib in vivo. Co-treatment inactivated ERK, transcriptionally downregulated SPHK1, and inactivated downstream AKT, p70 S6K and BAD, with inactivation abrogated by constitutive SPHK1 expression. The clinically applicable S1PR modulators fingolimod and mocravimod resensitize NRAS-mutated FLT3-ITD AML cells to FLT3 inhibitors, supporting potential clinical efficacy.

P1, N=10, Not yet recruiting, Ono Pharmaceutical Co., Ltd.

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 the TQT study, 42 subjects received single doses of pacritinib 400 mg, moxifloxacin 400 mg (positive control), and placebo in a crossover design. Median QTcF changes from pre-dose to 4 h post-dose were minimal (+2.7 and -0.3 ms, respectively), and no dose-response relationship was identified. These findings suggest that pacritinib exposure is unlikely to be correlated with QT prolongation.

P1, N=6, Not yet recruiting, Chengdu Zenitar Biomedical Technology Co., Ltd

P1/2, N=4, Terminated, The University of Texas Health Science Center at San Antonio | N=44 --> 4 | Trial completion date: Sep 2027 --> May 2026 | Recruiting --> Terminated | Trial primary completion date: Sep 2027 --> May 2026; Investigational drug limitations

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.