Ctni-19. Phase 2, Multicenter, Randomized Clinical Study to Evaluate the Efficacy and Safety of Safusidenib in Patients With High-Grade Isocitrate Dehydrogenase 1 (Idh1)-Mutant Glioma

Isocitrate dehydrogenase (IDH)-mutant gliomas are molecularly and clinically distinct cancers that affect primarily younger adults. Patients with World Health Organization (WHO) Grade 3 or Grade 4 IDH-mutant astrocytoma represent an unmet need because their disease inevitably progresses after current standard therapy (radiation or chemoradiation followed by adjuvant temozolomide), at which point salvage therapies provide nominal benefit. No targeted treatment is approved for WHO Grade 3 or Grade 4 IDH-mutant glioma. Safusidenib, a novel, potent, oral mutant IDH1 inhibitor, demonstrated promising phase 1 activity in patients with high-grade and contrast-enhancing IDH1-mutant glioma in a previous trial (NCT03030066). The current phase 2 trial (NCT05303519) evaluates the efficacy and safety of safusidenib in IDH1-mutant glioma in 2 parts. Part 1, which assessed safusidenib for recurrent/progressive disease, completed enrollment in December 2023. Recruitment for part 2 is anticipated to begin in 2025 and will include 100 adult patients with histologically confirmed IDH1-mutant Grade 3 or Grade 4 astrocytoma who had no evidence of tumor progression after biopsy and/or resection followed by radiation or chemoradiation, and at least 6 cycles of adjuvant temozolomide. Patients will be randomized 1:1 to receive either maintenance safusidenib 250 mg twice daily or placebo in 28-day cycles. The primary endpoint for part 2 is progression-free survival by blinded independent central review using RANO 2.0 criteria. Secondary endpoints include objective response rate, duration of response, overall survival, time to next intervention, investigator-assessed progression-free survival, and safety/tolerability.