Overview

Eligibility

Design Details

Arms & Interventions

Outcome Measures

Trial Sites

Source: NCT05765812

Recruiting

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

Interventional

Phase 1/2

Northwestern Memorial Hospital

Sponsor: Debiopharm

Last Updated: April 28, 2026

Notice- Information is sourced from public registries and may not reflect real-time changes at the local site.

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.

Treatment Category

Other Drugs, Chemotherapy, Radiation Therapy

Required Mutations

None

Trial Started

May 15, 2023

Last Updated by Sponsor

April 28, 2026

Estimated Completion

September 1, 2028

Contact Study

Name:Debiopharm International S.A

Email:clinicaltrials@debiopharm.com

Phone:+41 21 321 01 11

Eligibility

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.

Additional specific inclusion criteria for Phase 1 dose expansion and Phase 2:

Participants must have a histopathologically proven diagnosis of GBM, IDH-wildtype Grade 4 WHO 2021

Exclusion Criteria

Prior treatment with more than 2 lines of therapy for GBM, IDH-wildtype, Grade 4, or for astrocytoma, IDH-mutant, Grade 3

* 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.

* 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.

* Left ventricular ejection fraction (LVEF) below 55%.

* Prior radiation, chemotherapy, biological therapy, interstitial brachytherapy, implanted chemotherapy, therapeutics delivered by local injection or convection-enhanced delivery for GBM.

* Prior therapy that would result in an overlap of the radiation fields.

Additional specific exclusion 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 (based on WHO 2021). Combination therapy with TMZ and RT with or without subsequent TMZ maintenance treatment is considered as 1 systemic line.

[Note: Other inclusion/exclusion criteria mentioned in the protocol may apply.]

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Design Details

AllocationRandomized

Intervention ModelParallel Assignment

MaskingNone (Open Label)

Number to Enroll116

Arms & Interventions

Arms

Interventions

Type: Experimental

Description: Participants will receive intermittent Debio 0123, escalating doses along with temozolomide (TMZ) in each 28-day cycle for up to 2 years.

Interventions:

Debio 0123
Temozolomide
Radiotherapy

Outcome Measures

Primary Outcome Measures

Phase 1 (Dose Escalation): Number of Participants Experiencing Dose-limiting Toxicities (DLTs)Phase 1: Arm A: Cycle 1 (Cycle=28 days); Arms B and C: Up to approximately 1.8 months

Phase 1 (Dose Escalation): Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE)Up to 30 days after the end of treatment (Arm A: Up to approximately 26 months and Arms B and C: Up to approximately 3.5 months)

Phase 1 (Dose Escalation): Number of Participants With Clinically Significant Abnormalities in Laboratory, Vital Signs, Electrocardiogram (ECG), and Echocardiogram (ECHO) ParametersUp to 30 days after the end of treatment (Arm A: Up to approximately 26 months and Arms B and C: Up to approximately 3.5 months)

Phase 1 (Dose Escalation): Change From Baseline in Karnofsky Performance Status (KPS) ScoreUntil disease progression or end of study (approximately 66 months)

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): Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE)Up to approximately 26 months

Phase 1 (Dose Expansion): Change from Baseline in Tumor Size Assessed by Objective Response (OR) as per Response Assessment in Neuro-oncology (RANO) CriteriaFrom the start of study treatment until disease progression or end of study (up to approximately 66 months)

Phase 1 (Dose Expansion): Plasma Concentration of Debio 0123 and its MetabolitePredose and at multiple timepoints up to 6 hours post dose up to Day 15 of Cycle 1 (Cycle=28 days)

Phase 1 (Dose Expansion): Pharmacodynamic(s) PDy, Change from baseline in Phosphorylated Cell Division Cycle (pCDC2)Predose and 4 to 6 hours post dose on Day 10 of Cycle 1 (Cycle=28 days)

Phase 2: Overall Survival (OS)From the start of study treatment until death from any cause or end of study (up to approximately 66 months)

Secondary Outcome Measures

Phase 2: Number of Participants With At Least One TEAEUp to 30 days after the end of treatment (up to approximately 26 months)

Phase 2: Number of Participants With Clinically Significant Abnormalities in Laboratory, Vital Signs, and ECG ParametersUp to 30 days after the end of treatment (up to approximately 26 months)

Phase 1 (Dose Expansion): OSFrom the start of study treatment until death from any cause or end of study (up to approximately 66 months)

Phase 1 (Dose Escalation): Plasma Concentration of TemozolomidePhase 1: Predose and at multiple timepoints up to 7 hours post dose up to Day 5 of Cycle 1 (Arm A) and up to Day 29 (Arm B and C)

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)Up to 30 days after the end of treatment (up to approximately 26 months)

Phase 1 (Dose Expansion): Number of Participants With At Least one TEAEUp to 30 days after the end of treatment (up to approximately 26 months)

Phase 1 (Dose Expansion): Change From Baseline in KPS ScoreUntil disease progression or end of study (approximately 66 months)

Phase 2: Change From Baseline in KPS ScoreUntil disease progression or end of study (approximately 66 months)

Phases 1 and 2: Plasma Concentration of Debio 0123 and its MetabolitePhase1(Dose Escalation):Predose, multiple timepoints upto 8hours postdose upto Day 15 of Cycle 1(Arm A) and upto Day 29(Arms B and C);Phase1(Dose expansion)andPhase2: Predose, multiple timepoints upto 4hours postdose upto Day 15 of Cycle1(Cycle=28 days)

The pharmacokinetics (PK) of Debio-0123 and its metabolite will be evaluated in plasma.

Phases 1 and 2: Percentage of Participants With Best Overall Response (BOR) Assessed As Per Response Assessment in Neuro-oncology (RANO) CriteriaFrom the start of study treatment until disease progression or end of study (up to approximately 66 months)

Phases 1 and 2: Percentage of Participants with Objective Response (OR) Assessed As Per RANO CriteriaUp to end of study (approximately 66 months)

Phases 1 and 2: Percentage of Participants With Disease Control (DC) Assessed As Per RANO CriteriaFrom the start of study treatment until disease progression or end of study (up to approximately 66 months)

Phases 1 and 2: Duration of Response (DOR) Assessed As Per RANO CriteriaUp to disease progression or end of study (up to approximately 66 months)

Phases 1 and 2: Progression Free Survival (PFS) Assessed As Per RANO CriteriaFrom the start of study treatment until disease progression or death or end of study (up to approximately 66 months)

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Trial Sites

This study has 16 trial sites

Northwestern Memorial Hospital

Chicago, Illinois, US

Recruiting

Chicago, Illinois, 60611 US

Northwestern Memorial Hospital

Recruiting

Madrid, Madrid, 28041 ES

Hospital Universitario 12 de Octubre

Recruiting

Salt Lake City, Utah, 84112 US

Huntsman Cancer Institute

Recruiting

Seattle, Washington, 98109 US

Fred Hutchinson Cancer Research Center

Recruiting

València, València, 46010 ES

Hospital Clínico Universitario de Valencia

Recruiting

Houston, Texas, 77030 US

The University of Texas MD Anderson Cancer Center

Recruiting

New York, New York, 10016 US

New York University Langone Medical Center

Recruiting

San Antonio, Texas, 78229 US

South Texas Accelerated Research Therapeutics (START)

Recruiting

Barcelona, Barcelona, 8035 ES

Hospital Universitario Valle de Hebrón

Recruiting

Dallas, Texas, 75246 US

Baylor Scott & White Research Institute

Not yet recruiting

San Sebastián, Guipúzcoa, 20014 ES

Hospital Universitario Donostia

Recruiting

New York, New York, 10021 US

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

Recruiting

Pamplona, Navarra, 31008 ES

Clínica Universidad de Navarra

Recruiting

Madrid, Madrid, 28040 ES

Hospital Universitario Fundación Jiménez Díaz

Recruiting

Donostia / San Sebastian, 20014 ES

Hospital Universitario Donostia

Recruiting

Zurich, Zurich, 8091 CH

Universitätsspital Zürich

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