FLT3 mutation

In vivo, FLC-8 inhibited MV4-11 xenograft growth (TGI: 136-178% at 10-50 mg/kg) without overt toxicity. These findings identify Cys807 as a covalent binding hotspot in FLT3 and establish FLC-8 as a promising scaffold for next-generation FLT3 inhibitor development.

Moreover, F-17 showed potent selectivity and inhibition activity for FLT3-mutated cells both in vitro and in vivo. Collectively, the work provided a new insight for FLT3 inhibitor development.

Mechanistically, KD rewired anabolism toward fatty acid oxidation and glycine-utilizing pathways, modulated the expression of FLT3 signaling pathways and lipid biosynthesis, and promoted tumor cell differentiation. In conclusion, this study shows that KD reduces FLT3i resistance, offering a promising therapeutic solution.

P1, N=18, Recruiting, Memorial Sloan Kettering Cancer Center | N=36 --> 18

These results were confirmed in the CBF-2006 validation cohort. KIT-TKD mutations in RUNX1::RUNX1T1 and FLT3-ITD in CBFB::MYH11 worsen prognosis independently of MRD and must be included in risk stratification of CBF AMLs.

We evaluated the efficacy of a human TLK2 antisense oligonucleotide (ASO) alone and in combination with gilteritinib in AML cell lines...This study demonstrates that TLK2 ASO is a promising therapeutic strategy for AML, particularly in combination with FLT3 inhibition, and may apply to other TLK2-driven cancers. Future efforts should focus on improving ASO delivery and knockdown efficiency to maximize therapeutic benefit.

P1/2, N=606, Recruiting, Sumitomo Pharma America, Inc. | N=362 --> 606

In addition, when combined with clinically approved FLT3 inhibitors, GBA-16-24 exhibits synergistic anti-AML effects. Therefore, our findings introduce a promising ATR inhibitor and propose the combination of ATR and FLT3 inhibition as a novel synthetic lethal strategy for treating FLT3-mutated AML.

P1/2, N=366, Suspended, Curis, Inc. | Recruiting --> Suspended

P1/2, N=160, Recruiting, Sellas Life Sciences Group | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

All patients enrolled in phase II received induction and consolidation therapy with gilteritinib 120 mg/day plus chemotherapy (induction: ⩽2 cycles, idarubicin/cytarabine once-daily; consolidation: ⩽4 cycles, cytarabine twice-daily) followed by maintenance with gilteritinib 120 mg/day monotherapy (⩽26 cycles). Induction and consolidation with gilteritinib plus chemotherapy, and maintenance with gilteritinib monotherapy were well tolerated in ND patients in Asia with FLT3 mut+ AML and had favorable efficacy compared with historical data. This trial was registered with the ClinicalTrials.gov identifier NCT02310321.