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

NCT05765812 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: Debio 0123-GBM-1052022-502156-31U1111-1283-6423
• Study Type: interventional
• Target: 116
• Locations: 3 countries
• Sites: 17

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

Keywords

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

Outcome Measures

Primary Outcomes (9)

• 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) Parameters

  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

  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.

  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)

  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

  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

  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)

  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 Outcomes (14)

• Phase 1 (Dose Expansion): OS

  From 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 Temozolomide

  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)

• 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 TEAE

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

• Phase 1 (Dose Expansion): Change From Baseline in KPS Score

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

Study Arms (5)

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

EXPERIMENTAL

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

Drug: Debio 0123; Drug: Temozolomide

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

EXPERIMENTAL

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.

Drug: Debio 0123; Drug: Temozolomide; Radiation: Radiotherapy

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

EXPERIMENTAL

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

Drug: Debio 0123; Drug: Temozolomide; Radiation: Radiotherapy

Phase 1 (Dose Expansion): Debio 0123 + Temozolomide

EXPERIMENTAL

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.

Drug: Debio 0123; Drug: Temozolomide

Phase 2: Debio 0123 RD + Temozolomide

EXPERIMENTAL

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

Drug: Debio 0123; Drug: Temozolomide

Interventions

Debio 0123 DRUG

Administered as capsules.

Phase 1 (Dose Escalation): Arm A - Debio 0123 + Temozolomide; Phase 1 (Dose Escalation): Arm B - Debio 0123 + Temozolomide + Radiotherapy; Phase 1 (Dose Escalation): Arm C - Debio 0123 + Temozolomide + Radiotherapy; Phase 1 (Dose Expansion): Debio 0123 + Temozolomide; Phase 2: Debio 0123 RD + Temozolomide

Temozolomide DRUG

Administered as capsules.

Phase 1 (Dose Escalation): Arm A - Debio 0123 + Temozolomide; Phase 1 (Dose Escalation): Arm B - Debio 0123 + Temozolomide + Radiotherapy; Phase 1 (Dose Escalation): Arm C - Debio 0123 + Temozolomide + Radiotherapy; Phase 1 (Dose Expansion): Debio 0123 + Temozolomide; Phase 2: Debio 0123 RD + Temozolomide

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):

You may not qualify if:

• 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.

Sponsors & Collaborators

• Debiopharm International SA: lead

Study Sites (17)

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

RECRUITING

New York University Langone Medical Center

New York, New York, 10016, United States

RECRUITING

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

New York, New York, 10021, United States

RECRUITING

Baylor Scott & White Research Institute

Dallas, Texas, 75246, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, 78229, United States

RECRUITING

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

RECRUITING

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital Universitario Donostia

Donostia / San Sebastian, 20014, Spain

RECRUITING

Clinica Universidad de Navarra (CUN)

Madrid, 28027, Spain

RECRUITING

South Texas Accelerated Research Therapeutics (START)

Madrid, 28040, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Clinica Universidad de Navarra (CUN)

Pamplona, 31008, Spain

RECRUITING

Hospital Universitario Donostia

San Sebastián, 20014, Spain

NOT YET RECRUITING

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

Universitaetsspital Zuerich

Zurich, CH-8091, Switzerland

RECRUITING

MeSH Terms

Conditions

Astrocytoma; Glioblastoma; Lymphoma, Follicular

Interventions

Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Study Officials

• Study Director

  Debiopharm International SA

  STUDY DIRECTOR

Central Study Contacts

Debiopharm International S.A

CONTACT

+41 21 321 01 11; clinicaltrials@debiopharm.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 15, 2023
• First Posted: March 13, 2023
• Study Start: May 15, 2023
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (8); CH (1); US (8)