The FDA has granted fast track designation to the oral, selective mutant IDH1 inhibitor, safusidenib for the treatment of patients with IDH1-mutant glioma.1 The designation was supported by data from the safusidenib clinical development program, with most recently updated long-term follow-up data from the phase 2 J201 study (NCT04458272) in chemotherapy- and radiotherapy-naive grade 2 IDH1-mutant glioma.1,2
At a median follow-up of 38.8 months, patients who received safusidenib (n = 27) achieved a confirmed objective response rate (cORR) of 51.9%, a median progression-free survival (PFS) that was not reached, and a 36-month PFS rate of 79.1%.1,2 One patient who had responded experienced disease progression, and no new safety signals were identified.
"People with IDH1-mutant glioma urgently need additional treatment options. We were eager to pursue fast track designation for safusidenib to hopefully reach these patients on an expedited timeline," said David Hung, MD, president, and chief executive officer of Nuvation Bio, in a news release.1
The designation arrives as the pivotal phase 3 SIGMA study (NCT05303519) continues enrolling, evaluating safusidenib against placebo as maintenance therapy following standard-of-care in patients with IDH1-mutant, high-risk astrocytoma. A portion of the study is expected to enroll approximately 300 patients, alongside a separate, exploratory cohort of approximately 40 patients with grade 3 IDH1-mutant oligodendroglioma who have not yet received chemotherapy or radiotherapy.
The multicenter, Japanese study enrolled patients that were at least 20 years of age who had not recieved prior chemotherapy and radiotherapy for glioma except craniotomies or biopsies.3 Patients also needed to have IDH1-mutated grade 2 glioma per 2016 World Health Organization (WHO) classification, at least 1 measurable, non-enhancing lesion, an interval of 90 days or longer from their most recent surgery, no evidence of malignant transformation, and an ECOG performance status of 0 to 1.
If patients had grade 3 or 4 glioma per WHO classification, received prior treatment with other IDH1 inhibitors, active infections that required systemic treatment, multiple primary malignancies, a history of clinically significant cardiac disease, or recieved other investigational treatments within 28 days fo their first dose, they were not included in the trial.
All patients received twice daily, 250 mg doses of safusidenib on a continuous dosing schedule.
The primary end points of the trial were cORR per independent review committee and treatment-emergent adverse effects. Secondary end points for the trial included clinical benefit rate, time to response, duration of response, PFS, and overall survival.
Safusidenib is also being evaluated in additional studies as part of its development program.2 One of which is the randomized, phase 3 G307 trial (NCT07712757), evaluating safusidenib vs placebo in 140 patients with grade 2 IDH1-mutant glioma who have not yet received chemotherapy or radiation in regions where vorasidenib (Voranigo) is not yet approved or accessible. The primary end point for the study is PFS with ORR as the secondary end point.
Another is the phase 2 G209 trial (NCT07703436) which will enroll up to 40 patients in the US with grade 2 or 3 IDH1-mutant glioma that has progressed after treatment with vorasidenib with ORR as the primary end point.
