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

Patients meeting the eligibility criteria will be asked whether they are willing to participate in the study. After the consent has been signed, patients will be enrolled. They will then start treatment with safusidenib, 250 mg BID until disease progression, unacceptable toxicity, withdrawal of consent or at investigator discretion. A brain MRI will be performed every 2 months during the first 6 months and then every 3 months.

Inclusion criteria

• Male or female, age ≥18 years.
• 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.
• Karnofsky performance status of 70 or more.
• Adequate hematologic and organ functions.
• If taking corticosteroids, patients must be on a stable or decreasing dose for the 14 days prior first dose of study drug.
• 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.
• 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.
• 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

• Inability to undergo brain or spine MRI.
• Intent to be treated with radiotherapy or alkylating agent chemotherapy.
• Any investigational antitumor therapy other than those under investigation in this study.
• 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.
• Known hypersensitivity to safusidenib, to any drug with similar chemical structure, or to any other excipient present in the pharmaceutical form of safusidenib.
• 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).
• Subjects with history of significant cardiac disease within 12 months prior to first dose of study drug.
• 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 <400 copies/mL, CD4+ T-cell (CD4+) counts ≥350 cells/μL, an absence of opportunistic infections for the last 12 months, and participant agrees to be treated with anti-viral therapy for the duration of the study, if indicated.
• Subjects with acute or reactivated hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• Subjects with known history and/or serological evidence of chronic HBV infection will be included only if the following criteria are met: hepatitis B- deoxyribonucleic acid (DNA) viral load is below the limit of quantification, liver function tests meet inclusion criteria (AST, ALT, ALP, bilirubin), and participant agrees to be treated with anti-viral therapy for the duration of the study, if indicated.
• Subjects with known history and/or serological evidence of HCV infection will be included only if the following criteria are met: hepatitis C-ribonucleic acid (RNA) viral load is below the limit of quantification, liver function tests meet inclusion criteria (AST, ALT, ALP, bilirubin), and participant agrees to be treated with anti-viral therapy for the duration of the study, if indicated.
• Judgment by the investigator that the patient should not participate in the study because the patient is unlikely to comply with study procedures, restrictions and requirements. Only patients capable of judgment can be enrolled.
• Pregnancy or intention to become pregnant during the course of the study. WOCBP potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test.
• Women who are breast feeding and who do not agree to discontinue nursing prior to the first study treatment and for the period defined in the protocol.
• Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study.
• Concurrent malignancies unless the patient has been disease-free without intervention for at least one year.
• Concurrent use of other anti-cancer treatments or agents other than study medication.