ArticleNeuro-oncology2023
The first-in-human phase I study of a brain-penetrant mutant IDH1 inhibitor DS-1001 in patients with recurrent or progressive IDH1-mutant gliomas.
Article in Neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 2 registered trials, which are not on this map. Cited by 65 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1 Study of DS-1001b in Patients With IDH1 Mutated Gliomas
A Phase II Study of DS-1001b in Patients With Chemotherapy- and Radiotherapy-naive IDH1 Mutated WHO Grade II Glioma
Who cites it
65 citing papers in PubMed, 79 citations in OpenAlex.
- Phase II study of safusidenib erbumine in patients with chemotherapy- and radiotherapy-naïve isocitrate dehydrogenase 1-mutated WHO grade 2 gliomas.Neuro-oncology · 2026Trial
- Vorasidenib improves response to subsequent chemoradiation in a genetically engineered mouse model of IDH-mutant glioma.Science translational medicine · 2026Article
- Contemporary practice patterns in IDH-mutant glioma management: a multidisciplinary multi-institutional survey.Journal of neuro-oncology · 2026Article
- Current and emerging therapies in IDH-mutant glioma.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- The molecular profile of gliomas in adolescents and young adults.Neuro-oncology advances · 2026Review
- Review
- Recent Advances in Targeted Therapies for Adult Gliomas.Current neurology and neuroscience reports · 2026Review
- Radiographic Enhancing Progression Without Molecular or Histologic Progression in IDH-Mutant Grade 2 Astrocytoma Treated With an IDH Inhibitor: A Case Report.Case reports in neurological medicine · 2026Article
- New and Emerging Therapies for Patients with Low-Grade Glioma.CNS drugs · 2026Review
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
- Prickle4 Drives Microenvironmental Remodeling and Resistance to Parp Inhibition in IDH-Mutant Glioma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting IDH-driven Oncometabolism in glioblastoma: a computational approach for the identification of potential inhibitors.Frontiers in bioinformatics · 2026Article
- Review
- Single center experience of IDH inhibitors in recurrent high-grade gliomas.Journal of neuro-oncology · 2025Article
- Perioperative IDH inhibition in treatment-naive IDH-mutant glioma: a pilot trial.Nature medicine · 2025Article
- Review
- A scoping review of proton radiation therapy and mutant-isocitrate dehydrogenase-inhibitors in IDH mutated lower-grade gliomas: pushing beyond surrogate end-points.Acta neurochirurgica · 2025Article
- Advances in IDH-mutant glioma management: IDH inhibitors, clinical implications of INDIGO trial, and future perspectives.Future oncology (London, England) · 2025Review
- The role of vorasidenib in the treatment of isocitrate dehydrogenase-mutant glioma.Neuro-oncology · 2025Review
- Treatment of Isocitrate Dehydrogenase-Mutant Gliomas.Advances in oncology · 2025Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
25 authors at 11 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundApproximately 70% of lower-grade gliomas harbor isocitrate dehydrogenase 1 (IDH1) mutations, resulting in the accumulation of oncometabolite D-2-hydroxyglutarate (D-2-HG); this leads to epigenetic dysregulation, oncogenesis, and subsequent clonal expansion. DS-1001 is an oral brain-penetrant mutant IDH1 selective inhibitor. This first-in-human study investigated the safety, pharmacokinetics, pharmacodynamics, and efficacy of DS-1001.
methodsThis was a multicenter, open-label, dose-escalation, phase I study of DS-1001 for recurrent/progressive IDH1-mutant (R132) glioma (N = 47) (NCT03030066). DS-1001 was administered orally at 125-1400 mg twice daily. Dose-escalation used a modified continual reassessment method.
resultsThe maximum tolerated dose was not reached. Eight patients were continuing treatment at the data cutoff. Most adverse events (AEs) were grade 1-2. Twenty patients (42.6%) experienced at least 1 grade 3 AE. No grade 4 or 5 AEs or serious drug-related AEs were reported. Common AEs (>20%) were skin hyperpigmentation, diarrhea, pruritus, alopecia, arthralgia, nausea, headache, rash, and dry skin. The objective response rates were 17.1% for enhancing tumors and 33.3% for non-enhancing tumors. Median progression-free survival was 10.4 months (95% confidence interval [CI], 6.1 to 17.7 months) and not reached (95% CI, 24.1 to not reached) for the enhancing and non-enhancing glioma cohorts, respectively. Seven on-treatment brain tumor samples showed a significantly lower amount of D-2-HG compared with pre-study archived samples.
conclusionsDS-1001 was well tolerated with a favorable brain distribution. Recurrent/progressive IDH1-mutant glioma patients responded to treatment. A study of DS-1001 in patients with chemotherapy- and radiotherapy-naïve IDH1-mutated WHO grade 2 glioma is ongoing (NCT04458272).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.