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

NCT ID: NCT05765812

Last Updated: 2025-12-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

116 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-05-15

Study Completion Date

2028-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype Astrocytoma, Grade III

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

WEE1 inhibitor Glioblastoma, IDH-wildtype, Grade 4, World Health Organization (WHO) 2021 Astrocytoma, IDH-mutant, Grade 3, WHO 2021

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Parallel assignment applies to the arm groups within Phase 1 of the study. Sequential assignment will apply to Phases 1 and 2 of the study.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Phase 1 (Dose Escalation): Arm A - Debio 0123 + Temozolomide

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

Group Type EXPERIMENTAL

Debio 0123

Intervention Type DRUG

Administered as capsules.

Temozolomide

Intervention Type DRUG

Administered as capsules.

Phase 1 (Dose Escalation): Arm B - Debio 0123 + Temozolomide + Radiotherapy

Participants will receive intermittent Debio 0123, escalating doses along with TMZ and concomitant administration of radiotherapy (RT) for up to 6 weeks. As per Protocol \_V4.0 Arm B has been permanently halted.

Group Type EXPERIMENTAL

Debio 0123

Intervention Type DRUG

Administered as capsules.

Temozolomide

Intervention Type DRUG

Administered as capsules.

Radiotherapy

Intervention Type RADIATION

Administered 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): Arm C - Debio 0123 + Temozolomide + Radiotherapy

Participants will receive intermittent Debio 0123, escalating doses along with TMZ and concomitant administration of radiotherapy (RT) for up to 6 weeks.

Group Type EXPERIMENTAL

Debio 0123

Intervention Type DRUG

Administered as capsules.

Temozolomide

Intervention Type DRUG

Administered as capsules.

Radiotherapy

Intervention Type RADIATION

Administered 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 Expansion): Debio 0123 + Temozolomide

Participants will receive Debio 0123, escalating doses along with temozolomide (TMZ) in each 28-day cycle for up to 2 years. Participants will receive one of the 2 selected doses for further investigation.

Group Type EXPERIMENTAL

Debio 0123

Intervention Type DRUG

Administered as capsules.

Temozolomide

Intervention Type DRUG

Administered as capsules.

Phase 2: Debio 0123 RD + Temozolomide

Participants will receive intermittent Debio 0123 RD along with TMZ in each 28-day cycle for up to 2 years.

Group Type EXPERIMENTAL

Debio 0123

Intervention Type DRUG

Administered as capsules.

Temozolomide

Intervention Type DRUG

Administered as capsules.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Debio 0123

Administered as capsules.

Intervention Type DRUG

Temozolomide

Administered as capsules.

Intervention Type DRUG

Radiotherapy

Administered 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.

Intervention Type RADIATION

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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

Exclusion Criteria

* 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.


• 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Debiopharm International SA

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Study Director

Role: STUDY_DIRECTOR

Debiopharm International SA

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status RECRUITING

New York University Langone Medical Center

New York, New York, United States

Site Status RECRUITING

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

New York, New York, United States

Site Status RECRUITING

Baylor Scott & White Research Institute

Dallas, Texas, United States

Site Status RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, United States

Site Status RECRUITING

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status RECRUITING

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status RECRUITING

Hospital Universitario Donostia

Donostia / San Sebastian, , Spain

Site Status RECRUITING

Clinica Universidad de Navarra (CUN)

Madrid, , Spain

Site Status RECRUITING

South Texas Accelerated Research Therapeutics (START)

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status RECRUITING

Clinica Universidad de Navarra (CUN)

Pamplona, , Spain

Site Status RECRUITING

Hospital Universitario Donostia

San Sebastián, , Spain

Site Status NOT_YET_RECRUITING

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Site Status RECRUITING

Universitaetsspital Zuerich

Zurich, , Switzerland

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States Spain Switzerland

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Debiopharm International S.A

Role: CONTACT

Phone: +41 21 321 01 11

Email: [email protected]

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2022-502156-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1283-6423

Identifier Type: OTHER

Identifier Source: secondary_id

Debio 0123-GBM-105

Identifier Type: -

Identifier Source: org_study_id