IDH2 mutation

Overall, dapolsertib demonstrated modest single-agent activity in patients with AML. This trial was registered at www.clinicaltrials.gov as #NCT03008187.

P3, N=57, Active, not recruiting, Servier | Recruiting --> Active, not recruiting | Trial completion date: Jun 2031 --> Oct 2030 | Trial primary completion date: Jun 2026 --> Oct 2025

P1/2, N=51, Active, not recruiting, Institut de Recherches Internationales Servier | Recruiting --> Active, not recruiting

MAPK-pathway alterations represent a recurrent mechanism of resistance to mIDH1 inhibition in ICC, while emergent IDH1/IDH2 mutations appear infrequent. Functional data suggest that MAPK-mediated resistance may involve impaired IFN signaling. These results support MAPK-directed combination strategies and highlight the utility of ctDNA profiling to identify predictive and resistance biomarkers in mIDH1-driven ICC.

This study expands the genetic and morphologic repertoire of TCCRP with implications and pitfalls for accurate diagnosis. The findings highlight the IDH1/IDH2 dichotomy with convergence of phenotype in these rare breast tumours.

P1, N=18, Recruiting, Massachusetts General Hospital | Trial completion date: May 2025 --> Aug 2028 | Trial primary completion date: May 2024 --> Jan 2027

P2, N=42, Suspended, National Cancer Institute (NCI) | N=270 --> 42 | Recruiting --> Suspended

P1, N=78, Active, not recruiting, University of California, San Francisco | Recruiting --> Active, not recruiting

Docking and MM-GBSA analyses showed strong affinities with IDH1 (-14.2, -84.45 kcal/mol) and IDH2 (-16.8, -60.73 kcal/mol), exceeding those of reference inhibitors GSK321A (-9.6 kcal/mol) and Enasidenib (-8.9 kcal/mol)...This in silico study provides compelling evidence for Ternstroside D (CNP0166496) as a promising dual inhibitor for IDH1 and IDH2 mutations in AML. Furthermore, in vitro and in vivo studies are warranted to validate these findings.

P1, N=27, Recruiting, Washington University School of Medicine | N=12 --> 27

New therapeutic options to reduce the red blood cell (RBC) transfusion burden have emerged since 2020 and include luspatercept and imetelstat. Erythropoiesis-stimulating agents and lenalidomide also address anemia and are generally recommended to start at the time of transfusion dependency, although emerging data suggest that an earlier start of these interventions might offer clinical benefits...Targeted therapy directed to the presence of an IDH1 mutation is U.S. Food and Drug Administration (FDA) approved for the rare IDH1 mutated MDS (<10% of the time) and consideration to use an IDH2 inhibitor for IDH2 mutated MDS (<5% of the time) is reasonable. Interestingly, IDH mutations seem to appear with increased frequency in older patients and in patients with underlying autoimmune/rheumatological disorders.1.