A Study of Debio 0123 in Combination With Temozolomide in Adult Participants With Recurrent or Progressive Glioblastoma and of Debio 0123 in Combination With Temozolomide and Radiotherapy in Adult Participants With Newly Diagnosed Glioblastoma

Inclusion Criteria

• •Signed written informed consent approved before undertaking any study-specific procedures.
• •Age ≥18 years of age.
• •Willing to provide archived or fresh tumor sample, if available. Receipt of tumor sample is not required for the start of study treatment.
• •Adequate bone marrow, hepatic, and renal function.
• •Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
• •Willing to practice highly effective methods of contraception.
• •Life expectancy of at least 3 months in the best judgment of the Investigator.
• •Measurable or non-measurable disease as per RANO criteria by gadolinium (Gd)-based contrast-enhanced brain magnetic resonance imaging (MRI).
• •Participants receiving corticosteroids must be on a stable or decreasing dose of ≤4 mg daily dexamethasone (or ≤25 mg prednisone) for the 7 days prior to the start of study treatment.
• •Participants with seizures must be adequately controlled on a stable regimen of anti-epileptic drugs.
• •A maximum of 1 \[for Phase 1 (Dose Expansion) and phase 2\] or 2 (Phase 1 Arm A) prior treatment lines of which first-line must be treatment with TMZ-based chemoradiotherapy (TMZ concomitantly with RT).
• •Note: Only 1 prior line of systemic therapy is allowed; combination therapy with TMZ and RT with or without subsequent TMZ maintenance treatment is considered as 1 systemic line. Prior surgery, radiation, or localized delivery of therapeutic agents (i.e., carmustine-containing wafers \[GLIADEL®\]) for first recurrence is allowed.
• •Documented disease recurrence or progression by diagnostic biopsy or Gd-based contrast-enhanced brain MRI as per RANO criteria.
• •KPS ≥60.
• •Participants must have one of the following histopathologically proven diagnoses (WHO 2021):
• •GBM Isocitrate dehydrogenase (IDH)-wildtype Grade 4 which may include secondary GBMs (i.e., those that progress from low-grade gliomas).
• •Astrocytoma, IDH-mutant, Grade 3
• •Participants must have a new, histopathologically proven diagnosis of GBM, IDH-wildtype, Grade 4 (based on WHO 2021), which may include secondary GBMs (i.e., those that progress from low-grade gliomas) if the prior treatment included surgery only.
• •KPS ≥70.
• •Participants must have a histopathologically proven diagnosis of GBM, IDH-wildtype Grade 4 WHO 2021