96P OC201 and OC202e synergistically suppress EMT and metastasis by dual inhibition of PKCε–NFκB signaling and autophagy in pancreatic cancer

Background: Isocitrate dehydrogenase (IDH)-mutant gliomas are malignant, infiltrative brain tumors that are primarily diagnosed in young adults.Early clinical trials indicated that the IDH-1 inhibitor ivosidenib has clinical activity for treating IDHmutant glioma, leading to clinical use of this agent.Subsequently, the pan-IDH inhibitor vorasidenib was FDA-approved for the treatment of IDH-mutant grade 2 gliomas in 2024.We evaluated efficacy of vorasidenib in patients with prior exposure to ivosidenib. Methods:Retrospective review of patients with IDH-mutant glioma treated with vorasidenib who had prior treatment with ivosidenib.Prior treatments, radiographic response and adverse events were collected.Results: 29 patients (median age 41, 65.5% female) met inclusion criteria.Tumor types included IDH-mutant grade 2 astrocytoma (9, 31%), grade 3 astrocytoma (3, 10%), grade 4 astrocytoma (3, 10%), grade 2 oligodendroglioma (10, 34%) and grade 3 oligodendroglioma (4, 14%).Treatments received prior to ivosidenib included surgical resection (23, 79%), radiation (16, 55%), temozolomide (15, 52%), PCV (4, 14%) bevacizumab (3, 10%), lomustine (2, 7%) and pembrolizumab (1, 3%). 4 patients received additional treatment in between ivosidenib and vorasidenib treatment.16 patients transitioned from ivosidenib to vorasidenib due to tumor progression.10 achieved stable disease and are still undergoing treatment with vorasidenib; 6 had continued progression.11 patients transitioned from ivosidenib to vorasidenib when vorasidenib gained FDA approval.All 11 had continued disease stability.2 patients transitioned from ivosidenib to vorasidenib due to toxicity (diarrhea and fatigue).Both had resolution of toxicity and continued disease stability. Conclusions:Vorasidenib demonstrated clinical efficacy and tolerability in patients with IDH-mutant gliomas previously treated with ivosidenib.Notably, patients who transitioned due to FDA approval or toxicity maintained disease stability, while a subset of those with progression on ivosidenib achieved stabilization with vorasidenib.These findings support vorasidenib as a viable therapeutic option following ivosidenib exposure.