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Combining Debio 0123 with Temozolomide for Glioblastoma Treatment

A Phase 1/2 Open-label 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

Phase1; Phase2 Interventional Debiopharm International SA · NCT05765812

This study is testing if a new drug called Debio 0123, when combined with the standard treatment temozolomide, can help adults with glioblastoma feel better and improve their outcomes.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment116 (estimated)
Ages18 Years and up
SexAll
SponsorDebiopharm International SA Industry-sponsored
Drugs / interventionschemotherapy, radiation, prednisone
Locations17 sites (Chicago, Illinois and 16 other locations)
Trial IDNCT05765812 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and efficacy of Debio 0123, a WEE1 inhibitor, in combination with temozolomide for adults with recurrent or newly diagnosed glioblastoma. The study is divided into two phases: Phase 1 focuses on determining the appropriate dosage and identifying any dose-limiting toxicities, while Phase 2 will evaluate the effectiveness of the recommended dose compared to standard care. Participants will undergo treatment and monitoring to assess outcomes and tolerability.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with recurrent or newly diagnosed glioblastoma who meet specific health criteria.

Not a fit: Patients with significant comorbidities or those who are not able to comply with study protocols may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with glioblastoma, potentially improving survival rates and quality of life.

How similar studies have performed: Other studies have shown promise with similar approaches, but this specific combination is being evaluated for the first time.

Eligibility criteria

Show full inclusion / exclusion criteria 
Screening Inclusion Criteria for Phase 1 and Phase 2:

* 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.

Additional specific inclusion criteria for Phase 1 and Phase 2:

• 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.

Additional specific inclusion criteria for Phase 1 Arm A:

* 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

Additional specific inclusion criteria for Phase 1 Arm B and C:

* 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

Additional specific exclusion 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

Additional specific exclusion criteria for Phase 1 and Phase 2

* 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%.

Additional specific exclusion criteria for Phase 1 Arm B and C:

* 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.

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

Where this trial is running

Chicago, Illinois and 16 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Glioblastoma IDH WildtypeAstrocytoma, Grade IIIWEE1 inhibitorGlioblastoma, IDH-wildtype, Grade 4, World Health Organization 2021Astrocytoma, IDH-mutant, Grade 3, WHO 2021
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.