Recruiting
Phase 1
Phase 2

Debio 0123 & Temozolomide

Sponsor:

Debiopharm International SA

Code:

NCT05765812

Conditions

Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype

Astrocytoma, Grade III

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Debio 0123

Temozolomide

Radiotherapy

Study Details

Brief summary:

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.

Conditions

Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype

Astrocytoma, Grade III

Study ID

NCT05765812

Start date

May 15, 2023

Status verified date

Aug, 2026

Completion date

Sep, 2028

Anticipated

Primary completion date

Sep, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

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

Study Design

Enrollment

116 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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.

experimental: 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.

experimental: 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.

experimental: 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.

experimental: 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.

Interventions

Debio 0123

Administered as capsules.

Temozolomide

Administered as capsules.

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.

Primary outcome measure

  • Phase 1 (Dose Escalation): Number of Participants Experiencing Dose-limiting Toxicities (DLTs) [ Time Frame: 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) [ Time Frame: 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) Parameters [ Time Frame: 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): Change From Baseline in Karnofsky Performance Status (KPS) Score [ Time Frame: Until disease progression or end of study (approximately 66 months) ]
  • Phase 1 (Dose Expansion): Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE) [ Time Frame: 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) Criteria [ Time Frame: From 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 Metabolite [ Time Frame: Predose 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) [ Time Frame: Predose and 4 to 6 hours post dose on Day 10 of Cycle 1 (Cycle=28 days) ]
  • Phase 2: Overall Survival (OS) [ Time Frame: From the start of study treatment until death from any cause or end of study (up to approximately 66 months) ]

Central Contacts and Locations

Central contacts

Debiopharm International S.A

+41 21 321 01 11clinicaltrials@debiopharm.com

Locations

Northwestern Memorial Hospital

Recruiting

Chicago, Illinois, United States, 60611

New York University Langone Medical Center

Recruiting

New York, New York, United States, 10016

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

Recruiting

New York, New York, United States, 10021

Baylor Scott & White Research Institute

Recruiting

Dallas, Texas, United States, 75246

The University of Texas MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

South Texas Accelerated Research Therapeutics (START)

Recruiting

San Antonio, Texas, United States, 78229

Huntsman Cancer Institute

Recruiting

Salt Lake City, Utah, United States, 84112

Fred Hutchinson Cancer Research Center

Recruiting

Seattle, Washington, United States, 98109

More Information

Sponsor

Debiopharm International SA

Last update posted

Aug 24, 2026

Last verified

Aug, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Debiopharm International SA on 2026-08-24.