The primary purpose of the Phase 1 (Dose Escalation) of this study is to identify the dose-limiting toxicities (DLTs) of Debio 0123 combined with temozolomide (TMZ) (Arm A) and with TMZ and radiotherapy (RT) (Arms B and C) and to characterize the safety and tolerability of these combinations in adult participants with glioblastoma (GBM). Arm B which was previously added to the protocol, has been permanently halted per the safety monitoring committees' decision on the safety findings of this arm.
The primary purpose of Phase 1 (Dose expansion) of the study is to assess the doses studied under Phase 1 (Dose Escalation) Arm A and identify the recommended dose (RD) for further development.
The Phase 2 will start once the RD Phase 1 has been defined. The primary objective of Phase 2 is to assess the efficacy of Debio 0123 at the RD for further development in combination with TMZ, compared to the standard of care (SOC) in adult participants with GBM.
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.
Known contraindication to undergoing for Gd-based, contrast-enhanced MRI.
Any anticancer treatment, monoclonal antibodies/biologics, investigational treatment, or RT with curative intent within 28 days prior to starting study treatment.
Hypersensitivity to Debio 0123, TMZ, dacarbazine, or any of the excipients found in the formulation for Debio 0123 or TMZ.
Prior exposure to any WEE1 inhibitor.
Parallel
Debio 0123
DrugAdministered as capsules.
Temozolomide
DrugAdministered as capsules.
Radiotherapy
RadiationAdministered in accordance with the local clinical practice and applicable Radiation Therapy Oncology Group (RTOG) or the European Organization for Research and Treatment of Cancer (EORTC) guidelines.
Phase 1 (Dose Escalation): Number of Participants Experiencing Dose-limiting Toxicities (DLTs)
Phase 1 (Dose Escalation): Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE)
Phase 1 (Dose Escalation): Number of Participants With Clinically Significant Abnormalities in Laboratory, Vital Signs, Electrocardiogram (ECG), and Echocardiogram (ECHO) Parameters
Phase 1 (Dose Escalation): Change From Baseline in Karnofsky Performance Status (KPS) Score
KPS is an assessment tool for functional impairment. It is a standard way of measuring the ability of participants with cancer to perform ordinary tasks. The KPS scores range from 0 (death) to 100 (no evidence of disease). A higher score means the participant is better able to carry out daily activities.
Phase 1 (Dose Expansion): OS
Phase 1 (Dose Escalation): Plasma Concentration of Temozolomide
The PK of temozolomide will be evaluated in plasma.
Phase 1 (Dose Expansion): Number of Participants With Clinically Significant Abnormalities In Laboratory, Vital Signs, ECG, and (ECHO Parameters)
Phase 1 (Dose Expansion): Number of Participants With At Least one TEAE
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