Safusidenib Shows Robust, Ongoing Responses in Grade 2 IDH1-Mutant Glioma

Data from a phase 2 trial (NCT04458272) indicate that treatment with safusidenib erbumine (DS-1001b), a novel oral IDH inhibitor, may induce strong, durable responses and slow disease progression in treatment-naive patients with grade 2 IDH1-mutant gliomas.¹

The data, newly published in Neuro-Oncology, show a 44.4% confirmed objective response rate (ORR) among 27 chemotherapy- and radiotherapy-naive patients per Response Assessment in Neuro-Oncology (RANO) 2.0 criteria, meeting the trial’s primary end point.² Furthermore, the median progression-free survival (PFS) as of the data cutoff on March 10, 2023 had not been reached, with a 24-month event-free probability of 87.9%.

These efficacy results showcase the potency of this targeted, central nervous system-penetrant agent, offering the prospect of lasting disease control, delay of intensive chemoradiotherapy, and consequently improved quality of life for patients.

“Until recently, standard therapy for most IDH1-mutant gliomas was surgical resection followed by radiotherapy and chemotherapy, with only a subset of grade 2 patients undergoing active observation and delaying adjuvant chemoradiation and associated long-term toxicities,” said David Reardon, MD, Center for Neuro-Oncology at Dana-Farber Cancer Institute and study investigator, in a news release.¹ “While approved IDH-inhibitors can now also be used to delay chemoradiation, the durability of benefit remains inadequate for many patients, leaving a significant unmet need for providers and patients. The high rates and durability of responses seen in this trial suggest the potential for sustained disease control with safusidenib and support its further evaluation in IDH1-mutant gliomas.”

Additionally, a comment from Nuvation Bio, current developer of safusidenib, revealed that the agent’s benefits have persisted beyond the published data cutoff, further reinforcing its durability.

“While the published results reflect the March 10, 2023 data cutoff, as of September 15, 2025, 12 patients remained on treatment with safusidenib, further supporting the durability of responses. We look forward to sharing longer-term follow-up data in the future,” David Hung, MD, founder, president, and CEO of Nuvation Bio, added in the news release.¹

Safusidenib’s Safety Profile

Along with the promising efficacy findings, safusidenib exhibited a manageable safety profile, characterized by mostly mild to moderate adverse events (AEs). Treatment-emergent AEs were mostly grade 1 or 2; among the most frequent were alopecia (59.3%), arthralgia (55.6%), skin hyperpigmentation (48.1%), and alanine aminotransferase elevation (40.7%).

Five patients (18.5%) experienced grade ≥3 treatment-related AEs; 3 (11.1%) had treatment-related AEs that led to study treatment discontinuation, 2 of which were determined by investigators to be related to safusidenib and were resolved upon dose interruption and/or medical management.

Ongoing Clinical Evaluations of Safusidenib

The single-arm, open-label, multicenter phase 2 trial is active across 11 sites in Japan.³ The objective of the trial was to evaluate the efficacy and safety of safusidenib in patients with WHO grade 2 glioma harboring IDH1 mutations. For inclusion, patients must not have had prior anticancer therapy except for surgical resection or biopsy.

Meanwhile, a larger evaluation of safusidenib is underway in the multi-part G203 trial (NCT05303519) in high-grade IDH1-mutant gliomas, currently registered as a phase 2 study in locations across the US.⁴ A protocol amendment to finalize the study as a global phase 3 study is underway, which will support potential future regulatory submission.

The 2-part study features an expanded patient population to include patients with higher-grade gliomas. In part 1, the study will evaluate the efficacy, safety, and pharmacokinetic profile of safusidenib in up to 25 patients with recurrent or progressive IDH1-mutant grade 2 or grade 3 gliomas. The randomized, double-blind, part 2 portion will assess the efficacy of maintenance safusidenib treatment vs placebo in approximately 100 patients with IDH1-mutant grade 3 astrocytoma with high-risk features or grade 4 astrocytoma following standard-of-care radiation or chemoradiation and adjuvant temozolomide (Temodar). Here, the study will evaluate the primary end point of PFS assessed by blinded independent central review per RANO 2.0 criteria; secondary end points include overall survival, investigator-assessed PFS, ORR, duration of response, safety, and health-related quality of life.

Accrual for the G203 study is ongoing, with an estimated enrollment of 125 adult patients.

REFERENCES

1. Nuvation Bio announces publication of positive phase 2 study results for safusidenib for the treatment of grade 2 IDH1-mutant glioma in neuro-oncology. News release. Nuvation Bio. December 3, 2025. Accessed December 3, 2025. https://tinyurl.com/2p8yk8s6

2. Arakawa Y, Saito R, Kanemura Y, et al. Phase II study of safusidenib erbumine in patients with chemotherapy- and radiotherapy-naïve isocitrate dehydrogenase 1-mutated WHO grade 2 gliomas. Neuro-Oncology. Published online November 8, 2025. doi:10.1093/neuonc/noaf258

3. A study of DS-1001b in patients with chemotherapy- and radiotherapy-naive IDH1 mutated WHO grade II glioma. ClinicalTrials.gov. Updated March 18, 2025. Accessed December 3, 2025. https://clinicaltrials.gov/study/NCT04458272

4. Safusidenib phase 2 study in IDH1 mutant glioma. ClinicalTrials.gov. Updated November 21, 2025. Accessed December 3, 2025. https://www.clinicaltrials.gov/study/NCT05303519