Alexandra Miller, MD, PhD, Chief of Neuro-Oncology and Co-Director of the Brain and Spine Tumor Center at the Perlmutter Cancer Center at NYU Langone Health, discusses follow-up data on the safety and efficacy of safusidenib in patients with IDH-mutant gliomas.
Gliomas are the most common type of brain cancer in adults worldwide. IDH is a rare metabolic gene that causes tumor initiation in many gliomas and other cancers. IDH is necessary for the conversion of α-ketoglutarate (α-KG), however, when mutated, it reduces α-KG to oncometabolite D-2-hydroxyglutarate, causing elevated levels that can impact metabolism, cancer biology, and therapeutic sensitivity of gliomas. Approximately 2,500 patients in the U.S. are diagnosed with IDH-mutated Gliomas, of whom 95% of IDH1 mutations.
Recently, positive long-term follow-up data from the Phase 2 (J201) study of safusidenib in patients with chemotherapy- and radiotherapy-naïve grade 2 IDH1-mutant glioma were announced. Safusidenib is an investigational, oral, brain-penetrant, selective inhibitor of mutant IDH1.
The updated data includes 27 patients in Japan at a median of 38.8 months of follow-up. The centrally assessed confirmed overall response rate (ORR), per Response Assessment in Neuro-Oncology (RANO) for low grade gliomas (LGG) criteria, was 51.9%. Median progression-free survival (PFS) was not reached, and the 36-month PFS rate was 79.1%. Additionally, responses were durable, with only one patient who had previously responded experiencing subsequent disease progression. No new safety signals were identified.
Also announced were significant expansions of the clinical development program for safusidenib. Two new studies to evaluate safusidenib across the broader landscape of IDH1-mutant glioma will be initiated with the goal of evaluating safusidenib across the broader landscape of IDH1-mutant glioma and to provide an additional treatment option for patients whose cancer progresses after initial therapy and who wish to delay chemotherapy.
G307 (NCT07712757) is a phase 3, randomized, placebo-controlled study that will enroll approximately 140 patients with newly diagnosed grade 2 IDH1-mutant glioma who have not yet received chemotherapy or radiation. The study will be conducted at sites outside the US in regions where vorasidenib is not yet approved or accessible. The primary endpoint is PFS as assessed by blinded independent central review (BICR). Secondary endpoints include ORR, time to next intervention, duration of response, and time to response.
G209 (NCT07703436) is a phase 2, multicenter study that will enroll up to 40 patients in the US with grade 2 or 3 IDH1-mutant glioma who have experienced disease progression after treatment with vorasidenib and who remain in need of another option to delay radiation or chemotherapy. This study seeks to establish proof-of-concept for safusidenib in a setting of high unmet need. The primary endpoint is ORR by BICR, with a number of secondary endpoints, including tumor growth rate, an emerging way of assessing early anti-tumor activity.
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To learn more about IDH-mutant gliomas and other rare cancers, visit https://checkrare.com/diseases/cancers/