Voranigo (vorasidenib)

P=N/A, N=10, Not yet recruiting, Huashan Hospital

P1, N=60, Active, not recruiting, Institut de Recherches Internationales Servier | Recruiting --> Active, not recruiting

At the last follow-up, 3 years after vorasidenib discontinuation, the disease remained stable in 1 patient, while the other one had recurred. Vorasidenib does not appear to select an IDH-wildtype clone that would potentially reduce the tumor's sensitivity to standard therapies typically used in IDH-mutated glioma.

As a result, three repurposed drugs were identified as priorities: (i) mefloquine (reference drug: vorasidenib citrate), (ii) clofibric acid (reference drug: carmustine), and armillarisin A (reference drug: lomustine). These results also suggest repurposing candidates for synergistic combinations across different brain tumors. The two applications developed in this work are freely accessible and in the public domain at https://assay.smallmoles.com/escorwin.

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

In addition, treatments with the IDH-mutant inhibitors vorasidenib and ivosidenib further sensitize the cells to ferroptosis. Furthermore, dietary cysteine-methionine deprivation alone or in combination with convection-enhanced delivery of RSL3 or ivosidenib in vivo significantly prolongs survival of IDH1-mutant tumor-bearing mice. Our findings suggest that targeting cysteine and methionine metabolism in combination with IDH-mutant inhibition provides promising therapeutic strategies for IDH1-mutant gliomas.

Inhibitors of mutated IDH1 and IDH2, vorasidenib, ivosidenib, olutasidenib, and enasidenib, respectively, were recently approved by the FDA for relapsed/refractory AML. In this review, we mainly focus on IDH inhibitors in leukemia therapy, including the discovery, structure optimization, activity of IDH inhibitors, and applications, which provided the reference for the discovery of new anticancer agents.

P3, N=468, Recruiting, European Organisation for Research and Treatment of Cancer - EORTC | Not yet recruiting --> Recruiting

These results highlight the potential of ¹⁸F-DOPA-PET and advanced MRI sequences as valuable complements to standard RANO 2.0 MRI evaluations for assessing treatment response in glioma patients undergoing IDHi therapy.

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

P1, N=28, Completed, Institut de Recherches Internationales Servier (I.R.I.S.) | Recruiting --> Completed

P1/2, N=51, Active, not recruiting, Institut de Recherches Internationales Servier | Recruiting --> Active, not recruiting