P3, N=316, Not yet recruiting, Hutchmed

Currently, 3 targeted therapies are approved for use in CCA; Ivosidenib in patients with IDH1 mutations and Infigratinib/Pemigatinib in those with FGFR2 fusions. This is important, as it is thought up to 40 % of CCA patients harbour a potentially actionable mutation. In this review we provide an overview of the molecular pathogenesis of CCA and highlight currently available and potential future targeted treatments.

In HepG2 cells, the expressions of caspase-3, caspase-9, and p53 were significantly (p < 0.05) elevated. Overall, these findings suggest that chitosan coating of IVO-PLGA-NPs improves the delivery and efficacy of ivosidenib in liver cancer treatment.

One (5.3%) patient proceeded to a hematopoietic stem cell transplant by data cut-off. In conclusion, ivosidenib is clinically active, with durable remissions and a manageable safety profile observed in patients with mIDH1 R/R MDS.

P2, N=68, Active, not recruiting, Groupe Francophone des Myelodysplasies | Recruiting --> Active, not recruiting

Furthermore, mutations in NOTCH1 are associated with decreased astrocytic differentiation and may limit the response to IDHi. Our study highlights the differentiating potential of IDHi on the cellular hierarchies that drive oligodendrogliomas and suggests a genetic modifier that may improve patient stratification.

P3, N=146, Active, not recruiting, Institut de Recherches Internationales Servier | Trial completion date: Jun 2024 --> Jun 2026

The U.S. Food and Drug Administration (FDA) approved Ivosidenib, a molecular entity that targets IDH1 with R132 mutations, as a promising therapeutic option for AML with mIDH1 in 2018...RMSD showed that the four dynamics simulation systems remained stable, and RMSF and Rg showed that the screened molecules have similar local flexibility and tightness to the positive drug. Finally, the lowest energy conformation, hydrogen bond analysis, and free energy decomposition results indicate that in the entire system the key residues LEU120, TRP124, TRP267, and VAL281 mainly contribute van der Waals forces to the interaction, while the key residues VAL276 and CYS379 mainly contribute electrostatic forces.

Safety was consistent with the overall profile of olutasidenib. Olutasidenib offers a valuable treatment option for patients with mIDH1 AML previously treated with venetoclax.

P1, N=10, Active, not recruiting, Melbourne Health | Recruiting --> Active, not recruiting

Ivosidenib, used to treat acute myeloid leukemia, acts on a common cancer-linked variant of isocitrate dehydrogenase 1 (IDH1 R132H) inhibiting its "gain-of-function" activity-the undesired reduction of 2-oxoglutarate (2OG) to the oncometabolite 2-hydroxyglutarate (2HG)...Such details, essential for understanding inhibition mechanisms, are not readily resolved in conventional steady-state kinetics or by techniques that rely only on measuring binding. Extending the new method and analytical framework presented here to other enzyme systems will be straightforward and should rapidly reveal insight that is difficult or often impossible to obtain using other methods.

P1, N=95, Active, not recruiting, Institut de Recherches Internationales Servier | Trial completion date: Dec 2023 --> Mar 2024

Most patients (66.7%, n = 20) received drugs via the patient assistance program, with insurance initially covering a third of patients and with ongoing use, later covering 60%. Targeted therapies like IVO are options for mIDH glioma patients and can provide positive oncologic and neurological outcomes.

P2, N=21, Active, not recruiting, Servier | Recruiting --> Active, not recruiting | N=10 --> 21

P2, N=30, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

No abstract available

With advancements in molecular diagnostics and precision therapy, IDH inhibitors such as ivosidenib, vorasidenib and enasidenib are now mainstay in management of patients with a susceptible mutation. The Idyllaâ„¢ IDH1-2 Mutation Assay Kit (RUO) is a fully automated qPCR assay for the qualitative detection of 15 common mutations in IDH1 (R132C/H/G/S/L) and IDH2 (R140Q/L/G/W, R172K/M/G/W/S) at codon level. The Idyllaâ„¢ IDH1-2 Mutation Assay Kit demonstrates a high concordance with established reference methods across a range of different specimen types.

P1/2, N=84, Recruiting, M.D. Anderson Cancer Center | Phase classification: P1b/2 --> P1/2

P1, N=18, Not yet recruiting, University of Chicago

P1, N=49, Active, not recruiting, Institut de Recherches Internationales Servier | Trial completion date: May 2024 --> May 2025

P1, N=166, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Oct 2024 --> Oct 2025

orasidenib significantly advances LGG treatment, targeting a prevalent mutation and slowing tumor growth. Promising preclinical and clinical evidence and manageable side effects suggest its potential impact on LGG management. However, more research, including large trials, is needed to confirm its efficacy and role in treatment.

P1/2, N=336, Completed, Forma Therapeutics, Inc. | Active, not recruiting --> Completed

P1/2, N=69, Not yet recruiting, Australasian Leukaemia & Lymphoma Group

P1, N=75, Recruiting, Hutchmed | Trial completion date: Sep 2023 --> Jun 2025 | Trial primary completion date: Sep 2023 --> Sep 2024

P1, N=174, Completed, Institut de Recherches Internationales Servier | Active, not recruiting --> Completed

This study demonstrated that concomitant ivosidenib significantly reduced posaconazole and voriconazole levels. Voriconazole should be avoided, empiric high-dose posaconazole (>300 mg/day) may be considered, and therapeutic drug monitoring is recommended in all patients receiving concomitant ivosidenib.

P1, N=16, Completed, Institut de Recherches Internationales Servier | Recruiting --> Completed

P1, N=90, Active, not recruiting, Hutchmed | Recruiting --> Active, not recruiting

Once-daily ivosidenib 500 mg has a favorable PK/PD profile, attesting the 2-HG reduction mechanism of action and, thus, positive outcomes in treated patients with advanced mIDH1 cholangiocarcinoma.

No abstract available

P1/2, N=80, Recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

P=N/A, N=100, Recruiting, iOMEDICO AG | Not yet recruiting --> Recruiting

P2, N=49, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

P1/2, N=92, Recruiting, Servier Bio-Innovation LLC

P1, N=40, Not yet recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

P1/2, N=336, Active, not recruiting, Forma Therapeutics, Inc.

P=N/A, N=100, Not yet recruiting, iOMEDICO AG

P1, N=60, Completed, Eli Lilly and Company

P1, N=42, Completed, Eli Lilly and Company

P2, N=25, Active, not recruiting, Daiichi Sankyo Co., Ltd. | Trial primary completion date: Sep 2023 --> Mar 2023

P1, N=63, Recruiting, AnHeart Therapeutics Inc. | Not yet recruiting --> Recruiting