Phase II study of safusidenib erbumine in patients with chemotherapy- and radiotherapy-naïve isocitrate dehydrogenase 1-mutated WHO grade 2 gliomas

Background: Gliomas are primary brain tumors arising from glial cells. WHO grade 2 gliomas are initially managed with surgery for diagnosis and tumor reduction. However, complete resection is difficult due to their infiltrative growth into the normal brain and the need to preserve brain function. Current treatment options for WHO grade 2 gliomas are limited. Isocitrate dehydrogenase 1 (IDH1) mutations are frequently observed in WHO grade 2 gliomas. Safusidenib erbumine is a selective inhibitor of mutant IDH1 with substantial blood-brain barrier penetration. This study aimed to investigate the efficacy and safety of safusidenib erbumine in patients with chemotherapy- and radiotherapy-naïve IDH1-mutated WHO grade 2 gliomas. Methods: This phase II study implemented a multicenter, open-label, single-arm design and evaluated the efficacy and safety of safusidenib erbumine in 27 patients with chemotherapy- and radiotherapy-naïve IDH1-mutated WHO grade 2 gliomas (NCT04458272). Results: The confirmed objective response rate according to the Response Assessment in Neuro-Oncology criteria for WHO grade 2 gliomas was 44.4%. Median progression-free survival was not reached, with an event-free probability of 87.9% at 24 months. The frequently reported treatment-emergent adverse events (TEAEs) by Medical Dictionary for Regulatory Activities Preferred Terms (reported in ≥40%) were alopecia (59.3%), arthralgia (55.6%), skin hyperpigmentation (48.1%), and alanine aminotransferase increased (40.7%). Treatment-emergent adverse events were characterized as mostly grade 1 or 2. The incidence of treatment-related grade ≥3 TEAEs was 18.5%. Conclusions: Safusidenib erbumine is a potential treatment option for patients with chemotherapy- and radiotherapy-naïve IDH1-mutated WHO grade 2 gliomas.