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

Phase 1

Recruiting

• Conditions: Glioblastoma; MedDRA version: 20.0Level: PTClassification code: 10018336Term: Glioblastoma Class: 100000004864; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2022-502156-31-00
• Lead Sponsor: Debiopharm International S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-01-31
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

Phase 1 and Phase 2 Signed written informed consent approved before undertaking any study-specific procedures., Phase 1 and Phase 2 Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures., Additional specific criteria for Phase 1 Arm A Participants must have one of the following histopathologically proven diagnoses (WHO 2021) • GBM IDH-wildtype, Grade 4, which may include secondary GBMs (i.e., those that progress from low-grade gliomas) • Astrocytoma, IDH-mutant, Grade 3, Additional specific criteria for Phase 1 Arm B/C: Participants must have a new, histopathologically proven diagnosis (WHO 2021) of GBM, IDH-wildtype, Grade 4, which may include secondary GBMs (i.e., those that progress from low-grade gliomas)., Additional specific criteria for Phase 1 Arm A/dose expansion and Phase 2 A maximum of 1 (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), Additional specific criteria for Phase 1 Arm A/dose expansion and Phase 2 Documented disease recurrence or progression by diagnostic biopsy or Gd-based contrast-enhanced brain MRI as per RANO criteria., Additional specific criteria for Phase 1 Arm A/dose expansion and Phase 2 C) KPS =60., Additional specific criteria for Phase 1 Arm B/C B) KPS =70., Additional specific criteria for Phase 1 dose expansion and Phase 2 Participants must have a histopathologically proven diagnosis (WHO 2021) of GBM, IDH-wildtype, Grade 4., Phase 1 and Phase 2 Age =18 years of age., Phase 1 and Phase 2 Willing to provide archived or fresh tumor sample, if available. Receipt of tumor sample is not required for the start of study treatment., Phase 1 and Phase 2 Adequate bone marrow, hepatic, and renal function, Phase 1 and Phase 2 Life expectancy of at least 3 months in the best judgment of the Investigator, Phase 1 and Phase 2 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., Phase 1 and Phase 2 Participants with seizures must be adequately controlled on a stable regimen of anti-epileptic drugs., Phase 1 and Phase 2 Measurable or non-measurable disease per RANO criteria by gadolinium (Gd)-based contrast-enhanced brain magnetic resonance imaging (MRI)., Phase 1 and Phase 2 Willing to practice highly effective methods of contraception.

Exclusion Criteria

Phase 1 and Phase 2 History of other malignancies requiring active treatment in the last 2 years prior to the first dose of study treatment except for superficial bladder cancers, adequately treated low-risk prostate cancer under active surveillance, ductal carcinoma in situ or other carcinomas in situ, and non-melanoma skin cancers (basal cell/squamous cell skin cancer) that have been treated with curative intent., Specific criteria for Phase 1 Arm A Prior TMZ-related hematological event leading to discontinuation of TMZ during the concurrent chemoradiotherapy., Additional specific criteria for Phase 1 Arm B/C Prior radiation, chemotherapy, biological therapy, interstitial brachytherapy, implanted chemotherapy, therapeutics delivered by local injection or convection-enhanced delivery for GBM., Specific criteria for Phase 1 Arm B/C Prior therapy that would result in an overlap of the radiation fields., Additional specific criteria for Phase 1 dose expansion and Phase 2 Prior treatment with more than 1 line of systemic therapy for GBM, IDH-wildtype, Grade 4. Combination therapy with TMZ and RT with or without subsequent TMZ maintenance treatment is considered as 1systemic line, Phase 1 and Phase 2 Known contraindication for Gd-based, contrast-enhanced MRI., Phase 1 and Phase 2 Left ventricular ejection fraction (LVEF) below 55%., Phase 1 and Phase 2 Exposure to high levels of ultraviolet (UV) light, for example occupational exposure to sunlight or sunbathing., Phase 1 and Phase 2 Chemotherapy, monoclonal antibodies/biologics, investigational treatment, or RT with curative intent within 28 days prior to starting study treatment., Phase 1 and Phase 2 Hypersensitivity to Debio 0123, TMZ, dacarbazine, or any of the excipients found in the formulation for Debio 0123 or TMZ, Phase 1 and Phase 2 Prior exposure to any WEE1 inhibitor, Additional specific criteria for Phase 1 Arm A Prior treatment with more than 2 lines of therapy for GBM IDH-wildtype, Grade 4, or for astrocytoma, IDH-mutant, Grade 3., Specific criteria for Phase 1 Arm A Prior treatment with bevacizumab or with other vascular endothelial growth factor (VEGF) inhibitors or VEGF-receptor signaling inhibitors.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified