P1, N=36, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027

Results from the Japanese population enrolled in AGILE are aligned with those of the overall study. The efficacy of ivosidenib plus azacitidine in Japanese mIDH1 AML patients enrolled in AGILE who were ineligible for intensive chemotherapy appears to be consistent with the overall study population.

While not confirmatory, these findings may be clinically relevant in the context of this difficult-to-treat R/R IDH1m AML population.

In this report, we discuss the emerging role of mitochondrial metabolism as a target in IDH1-mutated CCA, including preclinical evidence supporting the inhibition of the tricarboxylic acid (TCA) cycle, glutamine metabolism, and potential combination approaches. We aim to highlight the growing need to integrate mitochondrial-targeted strategies into future clinical investigations.

Despite significantly prolonged progression-free survival, the mutant IDH1 inhibitor ivosidenib achieved only a 3% response rate in clinical trials, highlighting the need for new therapeutic options for IDH1mut iCCA...The combination of mIDH1 and MDM2 inhibitors synergistically suppressed the proliferation of IDH1wt iCCA cells. Our study delineated a novel mIDH1-MDM2-wtTP53 axis and its potential application of wtTP53 reactivation therapy in IDH1mut iCCA.

P1/2, N=50, Not yet recruiting, Fundacion PETHEMA

P3, N=220, Recruiting, Servier Affaires Médicales | Trial completion date: Jun 2025 --> Dec 2027 | Trial primary completion date: Jun 2025 --> Dec 2027

P1, N=20, Not yet recruiting, M.D. Anderson Cancer Center

P2/3, N=40, Recruiting, Frankfurter Institut Fuer Klinische Krebsforschung IKF GmbH

P2/3, N=247, Recruiting, Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

P1/2, N=60, Not yet recruiting, French Innovative Leukemia Organization

Using both clinical samples and experimental models, we demonstrate that the cell-permeable derivative dimethyl-α-ketoglutarate (DM-α-KG) exacerbates lipopolysaccharide (LPS)-induced tissue injury and cell death, whereas isocitrate dehydrogenase (IDH1) inhibition (IDH-305) or genetic ablation reduces α-KG levels and confers protection...These findings establish α-KG as a critical immunometabolic checkpoint in sepsis that licenses inflammatory cell death via TET2-mediated epigenetic control of AIM2. Our work not only elucidates a novel α-KG/TET2/AIM2 signaling axis in sepsis pathogenesis but also highlights the therapeutic potential of targeting this pathway to modulate immune responses.