Safusidenib Demonstrates Durable Responses in IDH1-Mutant Glioma and Advances Into Expanded Clinical Development

Clinical Summary:

• Design/Population: The phase 2 J201 study evaluated safusidenib, an oral brain-penetrant selective IDH1 inhibitor, in patients with grade 2 IDH1-mutant glioma.
• Key Outcomes: Safusidenib demonstrated durable antitumor activity, with an objective response rate of 51.9% and a 36-month progression-free survival rate of 79.1%. Median progression-free survival was not reached after a median follow-up of 38.8 months, and no new safety signals were identified. 
• Clinical Relevance: These findings support broader development of safusidenib across multiple IDH1-mutant glioma settings, including as maintenance therapy following chemoradiotherapy, treatment before radiation and chemotherapy, and therapy following progression on vorasidenib. 

Katherine Peters, MD, PhD, Preston Robert Tisch Brain Tumor Center, Durham, North Carolina, discusses results from the phase 2 J201 study evaluating safusidenib, an investigational, oral brain-penetrant selective IDH1 inhibitor, in patients with grade 2 IDH1-mutant glioma. 

Dr Peters reviews the durable responses and prolonged disease control observed with safusidenib and discusses how these findings have prompted an expanded clinical development program across multiple IDH1-mutant glioma settings. She highlights that ongoing studies will evaluate safusidenib as maintenance following standard chemoradiotherapy, before radiation and chemotherapy in newly diagnosed disease, and following progression on vorasidenib. She also discusses the potential role of targeted IDH1 inhibition in delaying traditional therapies and their associated long-term toxicities for younger patients with glioma.

Transcript:

Hello, my name is Dr Katherine Peters. I'm a neurologist and neuro-oncologist at the Preston Robert Tisch Brain Tumor Center, and I see mostly patients that have a tumor called a glioma.

It's the most common type of brain tumor for patients that can be malignant. In these patients, they can have a mutation specific to this tumor called isocitrate dehydrogenase-1, also known as IDH1. About 2,500 people are diagnosed with IDH1 glioma each year, and most of them will have this particular IDH1 gene mutation. 

These patients are usually diagnosed anywhere in their 30s to their 40s, and while people with this mutation can have a longer survival time than people that have a wild-type IDH glioma, that's usually called a glioblastoma, these tumors unfortunately can continue to grow and are not curable. We really need to find better treatments for these patients beyond standard chemo and radiation.

Today we're really discussing the very interesting results using an orally available, investigational, brain-penetrant selective inhibitor of mutant IDH1 known as safusidenib. This was evaluated in a recent phase 2 study labeled the J201 study. 

In this study, they evaluated 27 patients. It was performed in Japan, and it looked at patients that had grade II IDH mutant gliomas.

With a median follow-up of 38.8 months, they were able to evaluate overall response rate for these, and that was essentially 51.9%. Median progression-free survival has not even been reached yet, given that 38.8 months of follow-up. The 36-month PFS rate was 79.1%. The responses to safusidenib were very durable with only 1 patient who has previously responded experienced subsequent disease progression, and there were no new safety signals that were found.

What I think is important about this is with these really promising results of this drug in this space for these particular patients with an IDH1 mutation, it's really prompted to have these two new studies that will expand the potential of this drug in patients with IDH1 mutant gliomas.

One of the studies is the SIGMA study, this is G203 study. It's going to be a pivotal phase 3 study which will evaluate safusidenib compared to placebo as a maintenance therapy after patients complete standard-of-care radiation and chemotherapy in patients that have IDH1 mutant astrocytoma, particularly if they have high risk features. These high-risk features can include having more enhancement on the scan, maybe they have particular molecular markers which are associated with more high-risk features. This study is enrolling approximately around 300 patients. There's a separate exploratory cohort that will evaluate safusidenib in participants with grade III IDH1 mutant oligodendroglioma, which is a different tumor who have not yet received chemotherapy and radiotherapy. That primary end point is overall response rate. This is a cohort is expected to enroll around 40 patients.

It is so important to note that for these patients that are in their 30s to 40s, that we are trying to find ways to delay the use of radiation therapy or traditional chemotherapy because of the toxicities associated with these treatment paradigms, particularly with radiation therapy, the cognitive side effects that can come with this, and also with chemotherapy, with the cytotoxic effects of the classical chemotherapeutic agents, because these patients are in a unique stage of life where they're working, where maybe they're getting married, having families, definitely in a different transition phase. What I think is really important about safusidenib is they're thinking beyond just the last 2 studies that I mentioned, but also the studies, they have two other studies that are looking at ways to implement this drug in patients that have not received or have not yet received chemotherapy and radiation.

The first is the G307, it's a phase 3, randomized, placebo-controlled study that will enroll approximately 140 patients diagnosed with newly diagnosed grade II IDH1 glioma. This study will be particularly done outside of the US where vorasidenib, which is an FDA approved treatment, and is also approved in other countries where vorasidenib is not yet approved or accessible. This provides really a critical option for patients that are in need of these types of therapies other than traditional chemotherapy or radiation. The primary end point of this study will be progression-free survival by blinded independent central review.

Another study, and this is thinking more in the context that now we do have vorasidenib FDA approved, is what do we do after the use of vorasidenib? And in this study labeled G209, it is a phase 2 multi-centered study that will enroll up to 40 patients in the US that have either grade II or grade III IDH1 mutant glioma who have experienced disease progression after treatment with vorasidenib, but there still remains a need for another option before going to radiation and chemotherapy. This is truly a proof-of-concept study of safusidenib in this high unmet need area. The primary end point will be overall response as evaluated by a blind independent central review. There's a number of secondary end points including tumor growth rate along with assessing early anti-tumor activity. We're really excited to see what these unique studies will add to the landscape for these patients.

We're really excited about the next step and what the outlook will be for these two very important studies. We're looking forward to the future where we can use this targeted specific medication to help our patients with IDH1 mutant glioma.

Source:

Nuvation Bio. Nuvation Bio granted FDA Fast Track Designation for safusidenib for treatment of IDH1-mutant glioma. Accessed on: September 25, 2026. https://investors.nuvationbio.com/news/news-details/2026/Nuvation-Bio-Granted-FDA-Fast-Track-Designation-for-Safusidenib-for-Treatment-of-IDH1-Mutant-Glioma/default.aspx