Tibsovo (ivosidenib)

Current research has revealed that ASXL1 mutations in MDS predict demethylating agents (HMAs) resistance, the combination of HMAs and Venetoclax (VEN) achieved an ORR of 87%. DNMT3A R882 mutations induce decitabine sensitivity via hemi-methylated enhancer trapping, and TET2 mutations enhance HMAs efficacy only in ASXL1 wild-type contexts (ORR 62.1% vs. co-mutated 19%). RUNX1 aberrations reduce chemotherapy responses (18.9% ORR in high-risk MDS) through DNA repair impairment, while BCOR/EZH2 loss drives cytarabine resistance. TP53 multi-hit lesions correlate with poor survival (OS <12 months) but respond to eprenetapopt-azacitidine (ORR 73%), and IDH1/2 inhibitors achieve durable remissions (ivosidenib ORR 83.3%, mOS 35.7 months). In this paper, we systematically illustrate the correlation between key gene mutations and the response to HMAs, chemotherapy and targeted therapies in MDS patients. This article summarizes the current evidence on gene mutations as predictive biomarkers and discusses the direction of individualized therapy.

P2, N=1376, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2026 --> Jan 2027

P1, N=30, Not yet recruiting, Servier Bio-Innovation LLC | Initiation date: Sep 2025 --> Jan 2026

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.

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.

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.

P=N/A, N=8, Completed, iOMEDICO AG | Recruiting --> Completed | N=100 --> 8 | Trial completion date: Dec 2028 --> Jul 2025 | Trial primary completion date: Jun 2028 --> Jul 2025

This WES-AI-ML framework provides mutation-guided therapies for BC-CML, enabling real-time stratification and Food and Drug Administration-approved drug repurposing. While this exploratory study is limited by its small sample size (n = 7), it establishes a methodological framework for precision oncology stratification that warrants validation in larger, multi-center cohorts.

P2, N=40, Recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

P=N/A, N=250, Recruiting, French Innovative Leukemia Organisation | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Apr 2025 --> Aug 2025

ALIDHE represents, to our knowledge, the first AML clinical trial that involves patient representatives from development of the study concept to follow-up. ALAN will continue to be involved in ALIDHE as part of the patient steering committee, to ensure that patient perspectives and needs continue to be considered throughout the study duration.