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Glioblastoma IDH (Isocitrate Dehydrogenase) WildtypePhase 1/2NCT05765812

A Study of Zedoresertib (Debio 0123) in Combination With Temozolomide in Adult Participants With Recurrent or Progressive Glioblastoma and of Zedoresertib (Debio 0123) in Combination With Temozolomide and Radiotherapy in Adult Participants With Newly Diagnosed Glioblastoma

A Phase 1/2 study testing Zedoresertib, Temozolomide and Radiotherapy in people with Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype and Astrocytoma, Grade III, run by Debiopharm International SA at 16 sites in 3 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The primary purpose of the Phase 1 (Dose Escalation) of this study is to identify the dose-limiting toxicities (DLTs) of zedoresertib 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Zedoresertib, Temozolomide and Radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
116 participants
Where
16 sitesin 3 countries
Study dates
15 May 2023to Sep 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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 zedoresertib, TMZ, dacarbazine, or any of the excipients found in the formulation for zedoresertib 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.]

Trial locations and contacts

16 sites in 3 countries. Contact the study team or a site near you to ask about taking part.

Debiopharm International S.A contact

+41 21 321 01 11

clinicaltrials@debiopharm.com

16 sites in 3 countries

United States8 sites, 8 recruiting

  • Northwestern Memorial Hospital

    Chicago, Illinois, 60611

    Recruiting

  • Baylor Scott & White Research Institute

    Dallas, Texas, 75246

    Recruiting

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

    Recruiting

  • New York University Langone Medical Center

    New York, New York, 10016

    Recruiting

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

    New York, New York, 10021

    Recruiting

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

    Recruiting

  • South Texas Accelerated Research Therapeutics (START)

    San Antonio, Texas, 78229

    Recruiting

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

    Recruiting

Other trials in United States

Spain7 sites, 7 recruiting

  • Hospital Universitario Vall d'Hebron

    Barcelona, 08035

    Recruiting

  • Hospital Universitario Donostia

    Donostia / San Sebastian, 20014

    Recruiting

  • Clinica Universidad de Navarra (CUN)

    Madrid, 28027

    Recruiting

  • South Texas Accelerated Research Therapeutics (START)

    Madrid, 28040

    Recruiting

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

    Recruiting

  • Clinica Universidad de Navarra (CUN)

    Pamplona, 31008

    Recruiting

  • Hospital Clinico Universitario de Valencia

    Valencia, 46010

    Recruiting

Other trials in Spain

Switzerland1 site, 1 recruiting

  • Universitaetsspital Zuerich

    Zurich, CH-8091

    Recruiting

Other trials in Switzerland

About this study

Official title: 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

The primary purpose of the Phase 1 (Dose Escalation) of this study is to identify the dose-limiting toxicities (DLTs) of zedoresertib 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 zedoresertib at the RD for further development in combination with TMZ, compared to the standard of care (SOC) in adult participants with GBM.

Being tested
Zedoresertib, Temozolomide, Radiotherapy
Keywords
WEE1 inhibitor, Glioblastoma, IDH-wildtype, Grade 4, World Health Organization (WHO) 2021, Astrocytoma, IDH-mutant, Grade 3, WHO 2021
Medical subject headings
Astrocytoma, Glioblastoma, Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZedoresertibDrug

    Also called Debio 0123

    Administered as capsules.

  • TemozolomideDrug

    Administered as capsules.

  • RadiotherapyRadiation

    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.

Study groups in NCT05765812
Study groupRoleWhat they receive
Phase 1 (Dose Escalation): Arm A - Zedoresertib + TemozolomideExperimentalParticipants will receive intermittent zedoresertib, escalating doses along with temozolomide (TMZ) in each 28-day cycle for up to 2 years.
Receives: Drug: Zedoresertib; Drug: Temozolomide
Phase 1 (Dose Escalation): Arm B - Zedoresertib + Temozolomide + RadiotherapyExperimentalParticipants will receive intermittent zedoresertib, 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.
Receives: Drug: Zedoresertib; Drug: Temozolomide; Radiation: Radiotherapy
Phase 1 (Dose Escalation): Arm C - Zedoresertib + Temozolomide + RadiotherapyExperimentalParticipants will receive intermittent zedoresertib, escalating doses along with TMZ and concomitant administration of radiotherapy (RT) for up to 6 weeks.
Receives: Drug: Zedoresertib; Drug: Temozolomide; Radiation: Radiotherapy
Phase 1 (Dose Expansion): Zedoresertib + TemozolomideExperimentalParticipants will receive zedoresertib, 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.
Receives: Drug: Zedoresertib; Drug: Temozolomide
Phase 2: Zedoresertib RD + TemozolomideExperimentalParticipants will receive intermittent zedoresertib RD along with TMZ in each 28-day cycle for up to 2 years.
Receives: Drug: Zedoresertib; Drug: Temozolomide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1 (Dose Escalation): Number of Participants Experiencing Dose-limiting Toxicities (DLTs)

    Measured: Phase 1: Arm A: Cycle 1 (Cycle=28 days); Arms B and C: Up to approximately 1.8 months

  2. Phase 1 (Dose Escalation): Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE)

    Measured: 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)

  3. Phase 1 (Dose Escalation): Number of Participants With Clinically Significant Abnormalities in Laboratory, Vital Signs, Electrocardiogram (ECG), and Echocardiogram (ECHO) Parameters

    Measured: 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)

  4. 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.

    Measured: Until disease progression or end of study (approximately 66 months)

  5. Phase 1 (Dose Expansion): Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE)

    Measured: Up to approximately 26 months

  6. Phase 1 (Dose Expansion): Change from Baseline in Tumor Size Assessed by Objective Response (OR) as per Response Assessment in Neuro-oncology (RANO) Criteria

    Measured: From the start of study treatment until disease progression or end of study (up to approximately 66 months)

  7. Phase 1 (Dose Expansion): Plasma Concentration of Zedoresertib and its Metabolite

    Measured: Predose and at multiple timepoints up to 6 hours post dose up to Day 15 of Cycle 1 (Cycle=28 days)

  8. Phase 1 (Dose Expansion): Pharmacodynamic(s) PDy, Change from baseline in Phosphorylated Cell Division Cycle (pCDC2)

    Measured: Predose and 4 to 6 hours post dose on Day 10 of Cycle 1 (Cycle=28 days)

  9. Phase 2: Overall Survival (OS)

    Measured: From the start of study treatment until death from any cause or end of study (up to approximately 66 months)

Secondary outcomes (14)

  1. Phase 1 (Dose Expansion): OS

    Measured: From the start of study treatment until death from any cause or end of study (up to approximately 66 months)

  2. Phase 1 (Dose Escalation): Plasma Concentration of Temozolomide

    The PK of temozolomide will be evaluated in plasma.

    Measured: Phase 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)

  3. Phase 1 (Dose Expansion): Number of Participants With Clinically Significant Abnormalities In Laboratory, Vital Signs, ECG, and (ECHO Parameters)

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

  4. Phase 1 (Dose Expansion): Number of Participants With At Least one TEAE

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

  5. Phase 1 (Dose Expansion): Change From Baseline in 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.

    Measured: Until disease progression or end of study (approximately 66 months)

  6. Phase 2: Change From Baseline in 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.

    Measured: Until disease progression or end of study (approximately 66 months)

  7. Phase 2: Number of Participants With Clinically Significant Abnormalities in Laboratory, Vital Signs, and ECG Parameters

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

  8. Phase 2: Number of Participants With At Least One TEAE

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

  9. Phases 1 and 2: Plasma Concentration of Zedoresertib and its Metabolite

    The pharmacokinetics (PK) of zedoresertib and its metabolite will be evaluated in plasma.

    Measured: Phase1(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)

  10. Phases 1 and 2: Percentage of Participants With Best Overall Response (BOR) Assessed As Per Response Assessment in Neuro-oncology (RANO) Criteria

    Measured: From the start of study treatment until disease progression or end of study (up to approximately 66 months)

  11. Phases 1 and 2: Percentage of Participants with Objective Response (OR) Assessed As Per RANO Criteria

    Measured: Up to end of study (approximately 66 months)

  12. Phases 1 and 2: Percentage of Participants With Disease Control (DC) Assessed As Per RANO Criteria

    Measured: From the start of study treatment until disease progression or end of study (up to approximately 66 months)

  13. Phases 1 and 2: Duration of Response (DOR) Assessed As Per RANO Criteria

    Measured: Up to disease progression or end of study (up to approximately 66 months)

  14. Phases 1 and 2: Progression Free Survival (PFS) Assessed As Per RANO Criteria

    Measured: From the start of study treatment until disease progression or death or end of study (up to approximately 66 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Mar 2023
  2. Study start15 May 2023
  3. Primary completionSep 2028 (estimated)
  4. Study completionSep 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
None (open label)
Enrolment
116 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05765812
Sponsor's protocol ID
Debio 0123-GBM-105
Other IDs
2022-502156-31, U1111-1283-6423
Status last verified
Oct 2026
First submitted
15 Feb 2023
Last updated
28 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Zedoresertib, Temozolomide and Radiotherapy in people with Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype and Astrocytoma, Grade III, run by Debiopharm International SA at 16 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States, Spain, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Debiopharm International S.A (+41 21 321 01 11, clinicaltrials@debiopharm.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the 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). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05765812.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026.

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