Safusidenib Phase 2 Study in IDH1 Mutant Glioma

Open to people ages 18 years and up

for Part 1:

1. Patient must be ≥ 18 years of age at the time of signing the informed consent form (ICF).
2. Patient must have histologically confirmed recurrent or progressive WHO Grade 2 glioma or Grade 3 glioma with IDH1 R132H or R132C mutation confirmed by immunohistochemistry or molecular genetic testing.
3. The IDH mutation, and other applicable gene/molecular alterations (see Table 10-2) are determined by a validated assay as performed in Clinical Laboratory Improvement Amendments (CLIA)-certified/College of American Pathologists (CAP)-accredited or locally equivalent clinical laboratories. Prior clinical pathology report fulfilling the diagnosis criteria prior to screening with tumor samples collected is acceptable for patient enrollment in both Part 1 and Part 2.
4. Patient has received no more than 2 prior therapies for disease recurrence/progression.
5. Patient has disease recurrence or progression or cannot tolerate the most recent therapy.
6. Patient must have a measurable lesion(s) as per the RANO-HGG criteria for primarily enhancing lesions or RANO-LGG criteria for primarily non-enhancing lesions. The lesion (s) must be visible on 2 or more axial slices and have perpendicular diameters of at least 10 × 10 mm. The definition of primarily enhancing lesions or primarily non-enhancing lesions is referred to Section 8.3.1.

Key Inclusion Criteria for Part 2:

1. Must be ≥18 years old at the time of signing the ICF.
2. Diagnosis of histologically confirmed IDH1-mutant Grade 3 with high risk features or Grade 4 astrocytoma, per WHO 2021 classification and Investigator Assessment.
3. Have an IDH1 mutation (R132H/C/G/S/L) based on IHC (R132H only), polymerase chain reaction (PCR), or next-generation sequencing (NGS). CDKN2A/B status and at least 1 of the following must be confirmed: absence of 1p19q co-deletion by fluorescence in situ hybridization, array comparative genomic hybridization, or NGS; presence of an ATRX loss of function mutation by NGS; or loss of normal ATRX expression by IHC. A validated assay performed in a CLIA-certified/CAP-accredited (or local equivalent) clinical laboratory must be used for all of the aforementioned results. Documentation of biomarker status, including redacted molecular pathology and NGS reports, must be provided during Screening.
4. Must not have experienced disease recurrence or disease progression.
5. Participants must have completed radiation therapy with a minimum of 90% of planned treatment completed (with or without concurrent temozolomide) and between 6 and 12 cycles of adjuvant temozolomide and have no evidence of disease progression. Randomization must occur at least 28 days and not more than 75 days after the final dose of temozolomide.
6. Must agree to submit sufficient tumor tissue for retrospective biomarker and histological analyses. This requirement may be waived in rare circumstances with approval by the Sponsor.
7. Has adequate hematologic and organ functions

for Part 1:

• Prior anti-cancer therapy, within the applicable periods shown below, before the start of the protocol treatment:
• Systemic drug therapies: within 3 weeks (lomustine within 6 weeks)
• Surgery: within 3 weeks
• Radiation therapy: within 12 weeks
• Investigational agents: within 5 half-lives for other investigational agents
• Patient did receive the prior therapy targeted to IDH1 mutation..
• Known hypersensitivity to safusidenib or to any drug with similar chemical structure or to any other excipient present in the pharmaceutical form of safusidenib.

Key Exclusion Criteria for Part 2:

1. Participants may not have received any anticancer treatments other than surgery, radiation, concurrent/adjuvant temozolomide, and tumor-treating fields. Tumor-treating fields must be discontinued prior to randomization.
2. Participants with prior or anticipated treatment with anti-angiogenic agents such as Avastin (bevacizumab), agents known to target IDH1 or IDH2, or investigational agents for glioma are excluded.
3. Have brainstem or spinal cord involvement either as primary location, site of multifocal involvement, or by significant tumor extension.
4. Significant functional or neurocognitive deficits, including uncontrolled seizures, that would preclude participation in protocol-defined study activities, as assessed by Investigator.
5. Evidence of diffuse leptomeningeal disease by MRI.
6. History of significant cardiac disease within 12 months prior to randomization.
7. If taking corticosteroids, must be on a stable or decreasing dose for the 14 days prior to randomization.
8. Participants with other malignancies must have received curative treatment and been disease-free for at least 3 years. Curatively resected non-melanoma skin cancer or curatively treated carcinoma in situ is allowed.
9. Have a condition that would interfere with, or increase the risk of, study participation.