^
    6d
    A Study of an IDH1m Inhibitor in Participants With IDH1-Mutated Malignancies and Hepatic or Renal Impairment (clinicaltrials.gov)
    P1, N=30, Not yet recruiting, Servier Bio-Innovation LLC | Initiation date: Sep 2025 --> Jan 2026
    Trial initiation date
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
    |
    IDH1 R132
    |
    Tibsovo (ivosidenib)
    7d
    Autopalmitoylation of IDH1-R132H regulates its neomorphic activity in cancer cells. (PubMed, Nat Chem Biol)
    Interestingly, C269 autopalmitoylation occurs within a hydrophobic pocket, targeted by a clinical IDH1-mutant inhibitor (LY3410738). Our study reveals that autopalmitoylation, conferred by the IDH1R132H mutation, links fatty acid metabolism to the regulation of IDH1 mutant activity and represents a druggable vulnerability in IDH1-mutant cancers.
    Journal
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
    |
    IDH1 mutation • IDH wild-type • IDH1 R132
    |
    LY3410738
    10d
    Multiplexed Data-Independent Acquisition (mDIA) to Profile Extracellular Vesicle Proteomes. (PubMed, Mol Cell Proteomics)
    Results showed that library-based DIA, with project-specific spectral libraries generated from StageTip-based fractionation, outperformed other pipelines in protein identification and quantification. We demonstrated for the first time EV proteome landscape changes caused by the IDH1 mutation and inhibitor treatment in intrahepatic cholangiocarcinoma, highlighting the utility of mDIA in EV-based biomarker discovery.
    Journal
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
    |
    IDH1 mutation
    |
    Tibsovo (ivosidenib)
    10d
    Phase 3 Study of Vorasidenib (S095032/AG-881) in Asian Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 orIDH2 Mutation (clinicaltrials.gov)
    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
    Enrollment closed • Trial completion date • Trial primary completion date
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    IDH2 mutation • IDH1 R132 • IDH2 R172
    |
    Voranigo (vorasidenib)
    11d
    Drug-drug Interaction Study of Vorasidenib With Bupropion, Repaglinide, Flurbiprofen, Omeprazole, Midazolam, and Rosuvastatin in Healthy Adult Participants (clinicaltrials.gov)
    P1, N=28, Completed, Institut de Recherches Internationales Servier (I.R.I.S.) | Recruiting --> Completed
    Trial completion
    |
    Voranigo (vorasidenib) • midazolam hydrochloride • omeprazole
    11d
    Vorasidenib in Combination With Temozolomide (TMZ) in IDH-mutant Glioma (clinicaltrials.gov)
    P1/2, N=51, Active, not recruiting, Institut de Recherches Internationales Servier | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • ATRX (ATRX Chromatin Remodeler)
    |
    IDH2 mutation • CDKN2A deletion
    |
    temozolomide • Voranigo (vorasidenib)
    12d
    Olutasidenib With Azacitidine Followed by Olutasidenib Maintenance for the Treatment of IDH1-mutated Acute Myeloid Leukemia in Patients With Prior Treatment With Venetoclax Plus a Hypomethylating Agent (clinicaltrials.gov)
    P2, N=28, Recruiting, University of California, Davis | Not yet recruiting --> Recruiting
    Enrollment open
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
    |
    IDH1 R132 • Chr t(15;17)
    |
    Venclexta (venetoclax) • azacitidine • Rezlidhia (olutasidenib)
    21d
    Outcomes of Patients With IDH1-Mutated Myeloid Neoplasms Treated With Olutasidenib. (PubMed, Clin Lymphoma Myeloma Leuk)
    Olutasidenib-based therapy demonstrated 100% response rates in previously untreated IDH1-mutated AML and MDS and modest efficacy in heavily pretreated R/R AML and MDS. Durable remissions occurred in select responders and with stem cell transplant. Further evaluation of olutasidenib as frontline therapy in IDH1-mutated AML or MDS and as a bridge to transplant is warranted.
    Journal
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
    |
    IDH1 mutation
    |
    Venclexta (venetoclax) • Tibsovo (ivosidenib) • Rezlidhia (olutasidenib)
    22d
    MAPK Pathway Mutations Emerge in Mutant-IDH1 Inhibitor-Resistant Cholangiocarcinoma and Attenuate the Interferon Response. (PubMed, Clin Cancer Res)
    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.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • IFNG (Interferon, gamma)
    |
    KRAS mutation • NRAS mutation • IDH1 mutation • IDH2 mutation • ARID1A mutation
    |
    Tibsovo (ivosidenib)
    25d
    Olutasidenib With Azacitidine Followed by Olutasidenib Maintenance for the Treatment of IDH1-mutated Acute Myeloid Leukemia in Patients With Prior Treatment With Venetoclax Plus a Hypomethylating Agent (clinicaltrials.gov)
    P2, N=28, Not yet recruiting, University of California, Davis
    New P2 trial
    |
    Venclexta (venetoclax) • azacitidine • Rezlidhia (olutasidenib)
    1m
    Olutasidenib Single Plus Combo Therapy in IDH1mut AML After Induction and Consolidation (clinicaltrials.gov)
    P1, N=15, Not yet recruiting, Virginia Commonwealth University | Initiation date: Oct 2025 --> Feb 2026
    Trial initiation date
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
    |
    IDH1 mutation
    |
    Rezlidhia (olutasidenib)