Nuvation Bio Inc. (NYSE: NUVB) reported updated long-term data from the safusidenib clinical trial in IDH1-mutant glioma, alongside plans to launch two additional studies that would extend the drug's reach across a broader swath of the disease, including patients who have already progressed on a rival IDH inhibitor. The announcement expands the company's development strategy for safusidenib beyond the newly diagnosed setting to potentially address patients whose disease has progressed after first-line IDH-directed treatment, where there is no currently approved treatment option.
The updated figures come from J201, a Phase II study of safusidenib in 27 Japanese patients with chemotherapy- and radiotherapy-naïve grade 2 IDH1-mutant glioma. At a median follow-up of 38.8 months, the centrally assessed confirmed objective response rate reached 51.9%, per RANO low-grade glioma criteria. Median progression-free survival has not been reached, and the 36-month PFS rate stands at 79.1%. Only one patient who had previously responded went on to experience progression. Nuvation Bio said no new safety signals emerged with the additional year of follow-up.
Safusidenib is an oral, brain-penetrant, selective inhibitor of mutant IDH1 that blocks the enzyme's neomorphic production of the oncometabolite 2-hydroxyglutarate, a mechanism that disrupts normal cellular differentiation and drives gliomagenesis. Gliomas are the most common adult brain cancer, and IDH-mutant tumors account for roughly 2,500 US diagnoses annually, with more than 95% carrying an IDH1 mutation, typically in patients in their 30s and 40s.
Building on the J201 update, Nuvation Bio is launching two additional trials designed to address different points along the IDH1-mutant glioma treatment continuum. The first, G307, is a randomized, placebo-controlled Phase III study enrolling approximately 140 patients with newly diagnosed, treatment-naïve grade 2 IDH1-mutant glioma at sites outside the US, specifically in regions where vorasidenib is not yet approved or accessible. Its primary endpoint is progression-free survival by blinded independent central review, with objective response rate, time to next intervention, duration of response, and time to response as secondary measures.
The second, G209, is a Phase II, multicenter US study enrolling up to 40 patients with grade 2 or 3 IDH1-mutant glioma that has progressed following treatment with vorasidenib. Its primary endpoint is objective response rate by BICR, with tumor growth rate — an emerging early anti-tumor activity metric — among the secondary endpoints.
Both new studies sit alongside safusidenib's existing pivotal program, the ongoing Phase III SIGMA study, which is testing safusidenib as maintenance therapy after standard-of-care in IDH1-mutant astrocytoma with high-risk features in a roughly 300-patient pivotal cohort, plus a separate 40-patient exploratory cohort in treatment-naïve grade 3 oligodendroglioma.