Safusidenib Shows Durable Responses in IDH1-Mutant Glioma

Updated data from the J201 phase 2 study showed durable clinical activity with the investigational mutant IDH1 inhibitor safusidenib in patients with chemotherapy- and radiotherapy-naïve grade 2 IDH1-mutant glioma. The positive findings, announced by Nuvation Bio., were accompanied by plans to expand the clinical development program with 2 new studies evaluating safusidenib in newly diagnosed and post-vorasidenib IDH1-mutant glioma.¹

"We continue to be very encouraged by the longer-term data from our Phase 2 J201 study, and today's announcement marks a pivotal step forward in our mission to bring safusidenib as a comprehensive treatment option for patients with all types of IDH1-mutant glioma," David Hung, MD, founder, president, and chief executive officer of Nuvation, said in a statement.¹ “These two new studies are designed to evaluate safusidenib across a broader range of patients with IDH1-mutant glioma, with the ultimate goal of providing an effective therapy for nearly every patient with this disease."

Updated Phase 2 Data

The J201 study included 27 patients in Japan with grade 2 IDH1-mutant glioma who had not previously received chemotherapy or radiotherapy. At a median follow-up of 38.8 months, centrally assessed confirmed objective response rate (ORR), measured according to Response Assessment in Neuro-Oncology for low-grade glioma criteria, was 51.9%, while the 36-month progression-free survival (PFS) rate was 79.1%.

With an additional year of follow-up, responses continued to deepen and remained durable, with only 1 patient who had previously achieved a response subsequently experiencing disease progression. Additionally, median PFS was not reached. The updated findings also did not identify any new safety signals, with the safety profile remaining consistent with previous observations from the study.¹

Although the results suggest sustained disease control and tumor response with safusidenib, the J201 findings are limited by the small sample size and lack of a randomized comparator arm. Additional randomized studies will be needed to establish the efficacy of safusidenibrelative to standard treatment or placebo and to determine its potential role in clinical practice.

Expanding the Clinical Program

Based on the updated J201 data, Nuvation announced plans for 2 additional studies designed to evaluate safusidenib across broader populations of patients with IDH1-mutant glioma.The phase 3 G307 study (NCT07712757) will evaluate safusidenib in approximately 140 patients with newly diagnosed grade 2 IDH1-mutant glioma who have not previously received chemotherapy or radiotherapy. The randomized, placebo-controlled study will be conducted outside the United States in regions where vorasidenib is not yet approved or accessible. The primary endpoint will be PFS assessed by blinded independent central review, with secondary endpoints including ORR, time to next intervention, duration of response, and time to response.

The phase 2 G209 study (NCT07703436) will evaluate safusidenib in up to 40 patients in the United States with grade 2 or 3 IDH1-mutant glioma whose disease has progressed following treatment with vorasidenib. The study is intended to explore the potential activity of safusidenib in patients who have progressed on a prior mutant IDH1 inhibitor and remain in need of additional treatment options.The primary endpoint is ORR assessed by blinded independent central review. Secondary measures will include tumor growth rate (TGR), an emerging measure being investigated as a potential indicator of early antitumor activity, among other outcomes.¹

Clinical Context

IDH1 mutations are common in several types of glioma and are associated with distinct tumor biology and clinical characteristics. Although patients with IDH-mutant gliomas generally have more favorable survival outcomes than those with IDH-wild-type tumors, the disease remains incurable, and prognosis varies according to tumor grade and other high-risk features.

The therapeutic landscape for IDH-mutant glioma has evolved with the development of mutant IDH inhibitors. Vorasidenib, an oral, brain-penetrant inhibitor of mutant IDH1 and IDH2, has emerged as an important targeted treatment option for selected patients with grade 2 IDH-mutant glioma.² The availability of targeted therapy has also raised new questions regarding treatment sequencing and the management of disease following progression on an initial IDH inhibitor.

The G209 study is designed to address this emerging clinical question by evaluating safusidenib in patients whose disease has progressed following vorasidenib treatment.The study may provide early insight into whether sequential targeting of mutant IDH1 with a different investigational inhibitor can produce additional disease control following progression on prior targeted therapy.

Limitations and Next Steps

The updated J201 findings provide longer-term evidence of durable responses and disease control with safusidenib, but the study's small sample size, single-arm design, and enrollment of patients from a single country limit the ability to draw definitive conclusions regarding efficacy. The absence of a randomized comparator also makes it difficult to determine the extent to which outcomes differ from the natural history of IDH1-mutant glioma or from available treatment approaches.

The planned G307 phase 3 study will provide a randomized comparison in newly diagnosed grade 2 IDH1-mutant glioma in regions where vorasidenib is not yet approved or accessible. Meanwhile, the G209 phase 2 study will address an increasingly relevant clinical need by investigating treatment options for patients whose disease progresses following vorasidenib.

As targeted therapies become increasingly integrated into the management of IDH1-mutant glioma, the results of these studies may help clarify the role of sequential IDH inhibition and define how mutant IDH1 inhibitors can be incorporated across different stages of disease.

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. Nuvation Bio Inc. News Release. July 20, 2026. Accessed: July 29, 2026. https://investors.nuvationbio.com/news/news-details/2026/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/default.aspx
2. Mellinghoff IK, van den Bent MJ, Blumenthal DT, et al. Vorasidenib in IDH1- or IDH2-mutant low-grade glioma. N Engl J Med. 2023;389(7):589-601. doi:10.1056/NEJMoa2304194.