Safusidenib for Patients With Newly Diagnosed IDH1-mutant CNS WHO Grade 3 Oligodendroglioma and Astrocytoma - a Single Arm Phase II Study

The precise positioning of the emerging group of pharmacological inhibitors of mutant IDH enzymes remains to be refined by further studies and defined in national and international guidelines. The present study shall help to close this important knowledge gap when trying to define the role of mutant IDH inhibitors in the treatment algorithms for patients with IDH-mutant WHO grade 3 gliomas. Safusidenib is a novel, oral, potent, brain penetrant inhibitor of mutant IDH1. It has shown high blood brain barrier penetration in both pre-clinical and clinical studies and demonstrated anti-tumor activity with complete or partial responses. We aim at demonstrating the efficacy of safusidenib in patients with newly diagnosed IDH1-mutant CNS WHO grade 3 oligodendroglioma and astrocytoma, measured by progression-free survival at12 months.

Inclusion Criteria: 1. Male or female, age ≥18 years. 2. Newly diagnosed and histologically confirmed IDH1-mutant WHO grade 3 glioma, without or with residual disease: astrocytoma IDH1-mutant, or oligodendroglioma, IDH1-mutant and 1p/19q-codeleted, CNS WHO grade 3. IDH1 mutation can be defined by immunohistochemistry or by sequencing. Any location in the central nervous system is permitted. 3. Karnofsky performance status of 70 or more. 4. Adequate hematologic and organ functions. 5. If taking corticosteroids, patients must be on a stable or decreasing dose for the 14 days prior first dose of study drug. 6. Female patients must be either documented not to be Women of Childbearing Potential (WOCBP) or must have a negative pregnancy test within 14 days of starting treatment. Additionally WOCBP must agree to use, from the screening to at least 90 days following the last administration of safusidenib, highly effective contraception methods. Male subjects able to father children must agree to use two acceptable methods of contraception throughout the study and during at least 90 days following the last administration of safusidenib (e.g., condom with spermicidal gel). Double-barrier contraception is required. 7. Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and return for the required assessments. 8. Written informed consent for study participation must be signed and dated by the patient and the investigator prior to any study-related intervention. Exclusion Criteria: 1. Inability to undergo brain or spine MRI. 2. Intent to be treated with radiotherapy or alkylating agent chemotherapy. 3. Any investigational antitumor therapy other than those under investigation in this study. 4. Any severe concomitant condition including active and uncontrolled infections or other severe concurrent disease, which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol, in the opinion of the investigator. 5. Known hypersensitivity to safusidenib, to any drug with similar chemical structure, or to any other excipient present in the pharmaceutical form of safusidenib. 6. Subjects with a corrected QT interval by Fredericia's formula (QTcF) ≥470 milliseconds (msec) or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome). 7. Subjects with history of significant cardiac disease within 12 months prior to first dose of study drug. 8. Subjects with known human immunodeficiency virus (HIV) are ineligible unless the following criteria are met: have been receiving effective antiretroviral therapy for at least 4 weeks; viral load \