Ingo K Mellinghoff, Min Lu, Patrick Y Wen, Jennie W Taylor, Elizabeth A Maher, Isabel Arrillaga-Romany, Katherine B Peters, Benjamin M Ellingson, Marc K Rosenblum, Saewon Chun, Kha Le, Ania Tassinari, Sung Choe, Youssef Toubouti, Steven Schoenfeld, Shuchi S Pandya, Islam Hassan, Lori Steelman, Jennifer L Clarke, Timothy F Cloughesy
Vorasidenib and ivosidenib inhibit mutant forms of isocitrate dehydrogenase (mIDH) and have shown preliminary clinical activity against mIDH glioma. We evaluated both agents in a perioperative phase 1 trial to explore the mechanism of action in recurrent low-grade glioma (IGG) and select a molecule for phase 3 testing. Primary end-point was concentration of D-2-hydroxyglutarate (2-HG), the metabolic product of mIDH enzymes, measured in tumor tissue from 49 patients with mIDH1-R132H nonenhancing gliomas following randomized treatment with vorasidenib (50 mg or 10 mg once daily, q...
March 2023: Nature Medicine