Safusidenib Shows Durable Responses in IDH1-Mutant Glioma at 3-Year Follow-Up

Updated results from a phase 2 trial of safusidenib, an investigational oral IDH1 inhibitor, show that responses in patients with grade 2 IDH1-mutant glioma continued to deepen with longer follow-up, prompting the drug's developer to launch 2 additional trials that will test the agent earlier and later in the treatment sequence for this disease.¹

Nuvation Bio Inc announced on July 20 that updated data from the phase 2 J201 study, conducted in 27 patients in Japan with chemotherapy- and radiotherapy-naive grade 2 IDH1-mutant glioma, showed a centrally assessed confirmed objective response rate of 51.9% at a median follow-up of 38.8 months, per RANO criteria for low-grade glioma. Median progression-free survival (PFS) was not reached, and the 36-month PFS rate was 79.1%. Only 1 patient with a prior response had subsequently progressed, and no new safety signals were reported. The company said responses increased and deepened compared with earlier data cuts.

Safusidenib is a brain-penetrant, selective inhibitor of mutant IDH1 taken orally. Unlike vorasidenib (Voranigo), the only IDH1/2 inhibitor currently approved by the FDA for grade 2 astrocytoma or oligodendroglioma,² safusidenib targets IDH1 mutations exclusively.

Study Backgrounds

Building on the J201 data, Nuvation Bio said it will initiate 2 new studies designed to broaden the population of patients with IDH1-mutant glioma who could be treated with safusidenib.¹

The first, G307 (NCT07712757), is a randomized, placebo-controlled phase 3 trial that will enroll approximately 140 patients with newly diagnosed grade 2 IDH1-mutant glioma who have not yet received chemotherapy or radiation. The trial will be conducted outside the United States, in regions where vorasidenib is not yet approved or accessible. Its primary end point is PFS by blinded independent central review; secondary end points include objective response rate, time to next intervention, duration of response, and time to response.

The second, G209 (NCT07703436), is a phase 2, multicenter, US-based trial that will enroll up to 40 patients with grade 2 or 3 IDH1-mutant glioma whose disease has progressed after treatment with vorasidenib. The trial's primary end point is objective response rate by blinded independent central review, with tumor growth rate among the secondary end points.

"While the introduction of targeted therapies has transformed the treatment landscape for IDH1-mutant glioma, a critical question remains regarding sequencing of treatments once a patient progresses on a first-line inhibitor," said Macarena de la Fuente, MD, chief of the Neuro-Oncology Division and co-director of clinical neuro-oncology for the Brain Tumor Institute at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, said in a news release. "The G209 study is a vital step in addressing this clinical gap by evaluating the potential role of safusidenib in patients who have progressed on prior targeted therapy."

These studies join an existing pivotal phase 3 trial, SIGMA (G203; NCT05303519), which is evaluating safusidenib as maintenance therapy after standard-of-care treatment in IDH1-mutant astrocytoma with high-risk features, and enrolling approximately 300 patients. A separate, nonpivotal cohort within SIGMA is assessing safusidenib in patients with grade 3 IDH1-mutant oligodendroglioma who have not received chemotherapy or radiotherapy.

Clinical Necessity

IDH1-mutant gliomas account for a small but distinct subset of the roughly 2500 IDH-mutant gliomas diagnosed annually in the United States, with more than 95% of IDH-mutant tumors harboring an IDH1 rather than IDH2 mutation. These tumors typically arise in patients in their 30s and 40s and, while associated with longer survival than IDH wild-type gliomas, remain incurable, with prognosis worsening in the presence of high-risk features such as higher tumor grade.

REFERENCES

1. Nuvation Bio Announces Positive Updated Phase 2 Data and Expansion of Safusidenib Clinical Program with Two New Studies to Explore Broad Spectrum of IDH1-Mutant Glioma. News release. Nuvation Bio. July 20, 2026. Accessed July 20, 2026. https://tinyurl.com/ysccx4xa

2. FDA approves vorasidenib for Grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation. News release. FDA. August 6, 2024. Accessed August 6, 2024. https://tinyurl.com/3jv48wa9