Safusidenib Erbumine Shows Promise in Newly Diagnosed IDH1-Mutated Grade 2 Gliomas
Key Clinical Takeaways
- Design/Population: This phase 2 multicenter, open-label study evaluated safusidenib erbumine in 27 patients with newly diagnosed, chemotherapy- and radiotherapy-naïve WHO grade 2 IDH1-mutated gliomas. All patients received safusidenib erbumine monotherapy, and response was assessed using RANO criteria specific to WHO grade 2 gliomas.
- Key Outcomes: Safusidenib achieved a 44.4% confirmed objective response rate, with median PFS not reached and an event-free probability of 87.9% at 24 months. Common treatment-emergent adverse events included alopecia, arthralgia, skin hyperpigmentation, and elevated alanine aminotransferase, with most events being grade 1 or 2 in severity.
- Clinical Relevance: Safusidenib erbumine demonstrated promising efficacy and manageable toxicity in patients with untreated IDH1-mutated grade 2 gliomas. These findings support further development of this targeted therapy as a potential noncytotoxic treatment option in a population with limited therapeutic alternatives.
Results from a phase 2 study demonstrate that safusidenib erbumine, a selective mutant IDH1 inhibitor, shows promising clinical efficacy and safety among newly diagnosed patients with grade 2 IDH1-mutated gliomas.
According to Yoshiki Arakawa, MD, PhD, Kyoto University, Japan, and coauthors, “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,” leaving limited treatment options.
In this open-label, single-arm trial, 27 chemotherapy- and radiotherapy-naïve patients received 250 mg of twice daily safusidenib erbumine in 28-day cycles until treatment discontinuation. The primary end point was objective response rate (ORR). Key secondary end points included progression-free survival (PFS) and safety.
At a median follow-up of 28 months, the confirmed ORR was 44.4%. Median PFS was not reached, with a 24-month event-free probability of 87.9%. The most frequent treatment-emergent adverse events occurring in ≥40% of patients included alopecia (59.3%), arthralgia (55.6%), skin hyperpigmentation (48.1%), and increased alanine aminotransferase (40.7%). Grade ≥3 treatment-related adverse events were reported in 18.5% of patients.
“Safusidenib is a potential new treatment option for chemotherapy- and radiotherapy-naïve IDH1-mutated WHO grade 2 gliomas that can be used long-term, leading to delayed tumor recurrence and progression,” concluded Dr Arakawa et al. “The use of safusidenib as postoperative therapy prior to radiotherapy and chemotherapy allows these therapies to be deferred until recurrence, thereby delaying toxicities and potentially prolonging survival.”
Source:
Arakawa Y, Saito R, Kanemura Y, et al. Phase II study of safusidenib erbumine in patients with chemotherapy- and radiotherapy-naïve isocitrate dehydrogenase 1-mutated WHO grade 2 gliomas. Neuro-Oncology. Published online: November 8, 2025. doi:10.1093/neuonc/noaf258
