Glioblastoma Treatment With Irradiation and Olaptesed Pegol (NOX-A12) in MGMT Unmethylated Patients

NCT04121455 | Active Not Recruiting Phase 1

• 3 other identifiers: SNOXA12C4012024-510964-21-002018-004064-62
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to obtain first, exploratory information on the safety and efficacy of (i) olaptesed pegol in combination with radiation therapy in patients with newly diagnosed glioblastoma of unmethylated MGMT promoter status either not amenable to resection (biopsy only) or after incomplete tumor resection, and (ii) olaptesed pegol in combination with radiation therapy and bevacizumab in patients with newly diagnosed glioblastoma of unmethylated MGMT promoter status either not amenable to resection (biopsy only) or after incomplete or complete tumor resection. Further arms are included (i) to establish safety for the combination of olaptesed pegol at three different doses in addition to radiotherapy and bevacizumab, (ii) to explore the benefit of combining olaptesed pegol at different dose levels with bevacizumab in order to define the doses to move forward into a subsequent randomized dose-finding study, (iii) to explore the contribution of the therapy components olaptesed pegol and bevacizumab to patient benefit and (iv) to put the clinical outcome of these treatment regimens into perspective with the standard of care treatment with temozolomide and radiotherapy.

Conditions

Glioblastoma

Keywords

Glioblastoma; NOX-A12; Olaptesed pegol; Spiegelmer; Stromal cell-derived factor-1 (SDF-1); CXCL12; Radiation; MGMT promoter; Brain tumor; Radiotherapy; Brain cancer; Tumor microenvironment; Bevacizumab

Outcome Measures

Primary Outcomes (1)

• Safety - Number of patients with treatment-related adverse events as assessed by CTCAE

  Number of patients with treatment-related adverse events as assessed by CTCAE

  through study completion, an average of 3 years

Secondary Outcomes (10)

• Efficacy - progression free survival at 6 months (PFS-6)

  6 months

• Efficacy - Median progression-free survival (mPFS)

  until end of treatment, an average 1 year

• Efficacy - Median overall survival (mOS)

  through study completion, an average of 3 years

• Efficacy - Landmark overall survival at 18 months (OS18)

  18 months

• Overall response rate (ORR)

  through study completion, an average of 3 years

Study Arms (11)

Cohort 1: 200 mg Olaptesed pegol + Radiotherapy

EXPERIMENTAL

olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6

Drug: Olaptesed pegol; Radiation: Radiotherapy

Cohort 2: 400 mg Olaptesed pegol + Radiotherapy

EXPERIMENTAL

olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6

Drug: Olaptesed pegol; Radiation: Radiotherapy

Cohort 3: 600 mg Olaptesed pegol + Radiotherapy

EXPERIMENTAL

olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6

Drug: Olaptesed pegol; Radiation: Radiotherapy

Expansion group, Arm A: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab

EXPERIMENTAL

olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion, bevacizumab every two weeks for 26 weeks plus radiotherapy during weeks 1-6, incompletely or not resected patients

Drug: Olaptesed pegol; Radiation: Radiotherapy; Drug: Bevacizumab

Expansion group, Arm B: 600 mg Olaptesed pegol + Radiotherapy

EXPERIMENTAL

olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6, completely resected patients

Drug: Olaptesed pegol; Radiation: Radiotherapy

Expansion group, Arm C: 600 mg Olaptesed pegol + Radiotherapy + 200 mg Pembrolizumab

EXPERIMENTAL

olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion, pembrolizumab every three weeks for 26 weeks plus radiotherapy during weeks 1-6, incompletely resected patients

Drug: Olaptesed pegol; Radiation: Radiotherapy; Drug: Pembrolizumab

Expansion group, Arm D: 200 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab

EXPERIMENTAL

olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients

Drug: Olaptesed pegol; Radiation: Radiotherapy; Drug: Bevacizumab

Expansion group, Arm E: 400 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab

EXPERIMENTAL

olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients

Drug: Olaptesed pegol; Radiation: Radiotherapy; Drug: Bevacizumab

Expansion group, Arm F: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kgBevacizumab

EXPERIMENTAL

olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients

Drug: Olaptesed pegol; Radiation: Radiotherapy; Drug: Bevacizumab

Expansion group, Arm G: 600 mg Olaptesed pegol + Radiotherapy

EXPERIMENTAL

olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients

Drug: Olaptesed pegol; Radiation: Radiotherapy

Expansion group, Arm H: Standard of care - Temozolomide + Radiotherapy

ACTIVE COMPARATOR

oral treatment up to 35 weeks according to current SPC

Radiation: Radiotherapy; Drug: Temozolomide (TMZ)

Interventions

Olaptesed pegol DRUG

Olaptesed pegol continuous i.v. administration

Also known as: NOX-A12

Cohort 1: 200 mg Olaptesed pegol + Radiotherapy; Cohort 2: 400 mg Olaptesed pegol + Radiotherapy; Cohort 3: 600 mg Olaptesed pegol + Radiotherapy; Expansion group, Arm A: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab; Expansion group, Arm B: 600 mg Olaptesed pegol + Radiotherapy; Expansion group, Arm C: 600 mg Olaptesed pegol + Radiotherapy + 200 mg Pembrolizumab; Expansion group, Arm D: 200 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab; Expansion group, Arm E: 400 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab; Expansion group, Arm F: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kgBevacizumab; Expansion group, Arm G: 600 mg Olaptesed pegol + Radiotherapy

Radiotherapy RADIATION

Radiotherapy in weeks 1-6; cumulative dose of 60 Gy in 2 Gy fractions

Cohort 1: 200 mg Olaptesed pegol + Radiotherapy; Cohort 2: 400 mg Olaptesed pegol + Radiotherapy; Cohort 3: 600 mg Olaptesed pegol + Radiotherapy; Expansion group, Arm A: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab; Expansion group, Arm B: 600 mg Olaptesed pegol + Radiotherapy; Expansion group, Arm C: 600 mg Olaptesed pegol + Radiotherapy + 200 mg Pembrolizumab; Expansion group, Arm D: 200 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab; Expansion group, Arm E: 400 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab; Expansion group, Arm F: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kgBevacizumab; Expansion group, Arm G: 600 mg Olaptesed pegol + Radiotherapy; Expansion group, Arm H: Standard of care - Temozolomide + Radiotherapy

Bevacizumab DRUG

Bevacizumab every 2 weeks i.v. infusion

Expansion group, Arm A: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab; Expansion group, Arm D: 200 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab; Expansion group, Arm E: 400 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab; Expansion group, Arm F: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kgBevacizumab

Pembrolizumab DRUG

Pembrolizumab every 3 weeks i.v. for 26 weeks

Also known as: KEYTRUDA

Expansion group, Arm C: 600 mg Olaptesed pegol + Radiotherapy + 200 mg Pembrolizumab

Temozolomide (TMZ) DRUG

oral treatment according to current SPC

Expansion group, Arm H: Standard of care - Temozolomide + Radiotherapy

Eligibility Criteria

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

You may qualify if:

• Written informed consent
• Age ≥18 years
• Patient agreement to diagnostic and scientific work-up of glioblastoma tissue obtained during the preceding surgery or biopsy
• Patient agrees to subcutaneous port implantation
• Newly diagnosed, histologically confirmed, supratentorial WHO grade IV glioblastoma
• Status post biopsy or incomplete resection
• Unmethylated MGMT promoter status
• Maximum Eastern Cooperative Oncology Group (ECOG) score 2
• Estimated minimum life expectancy 3 months
• The following laboratory parameters should be within the ranges specified:
• Total bilirubin ≤ 1.5 x upper limit normal (ULN)
• Creatinine ≤ 1.5 x ULN or glomerular filtration rate ≥ 60 mL/min/1.73m²
• ALT (alanine transaminase) ≤ 3 x ULN
• AST (aspartate transaminase) ≤ 3 x ULN
• Female patients of child-bearing potential must have a negative serum pregnancy test within 21 days prior to enrollment and agree to use a highly effective method of birth control (failure rate less than 1% per year when used consistently and correctly such as contraceptive implants, vaginal rings, sterilization, or sexual abstinence)" during and for 3 months following last dose of drug (more frequent pregnancy tests may be conducted if required per local regulations)

You may not qualify if:

• Inability to understand and collaborate throughout the study or inability or unwillingness to comply with study requirements
• Participation in any clinical research study with administration of an investigational drug or therapy within 30 days from screening visit or observation period of competing studies
• Contra-indication or known hypersensitivity to MRI contrast agents, olaptesed pegol or polyethylene glycol
• Cytostatic therapy (chemotherapy) within the past 5 years
• History of other cancers (except for adequately treated basal or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the patient was disease-free for ≥ 5 years)
• Clinically significant or uncontrolled cardiovascular disease
• Prior radiotherapy to the head
• Any other previous or concomitant experimental glioblastoma treatments
• Placement of Gliadel® wafer, seeds, or ferromagnetic nanoparticles
• Pregnancy or lactation
• Uncontrolled intercurrent illness; patients must be free of any clinically relevant disease (other than glioma) that would, in the treating investigator\'s opinion, interfere with the conduct of the study or study evaluations
• Treatment not initiated within 6 weeks after first biopsy or surgery of glioblastoma
• Prior enrolment into this study
• Inability to understand and collaborate throughout the study or inability or unwillingness to comply with study requirements
• Participation in any clinical research study with administration of an investigational drug or therapy within 30 days from screening visit or observation period of competing studies

Sponsors & Collaborators

• TME Pharma AG: lead

Study Sites (6)

Klinik und Poliklinik für Neurologie Schwerpunkt Klinische Neuroonkologie

Bonn, Germany

Location

Klinik für Neurologie

Essen, Germany

Location

Klinik für Strahlentherapie und Radioonkologie

Leipzig, Germany

Location

Klinik für Strahlentherapie und Radioonkologie

Mannheim, Germany

Location

Klinik für Neurologie mit Institut für Translationale Neurologie

Münster, Germany

Location

Abteilung Neurologie mit interdisziplinärem Schwerpunkt Neuroonkologie

Tübingen, Germany

Location

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

NOX-A12; Radiotherapy; Bevacizumab; pembrolizumab; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

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: 3+3 dose escalation (sequential) followed by a multiple-arm expansion group (parallel)

Study Record Dates

• First Submitted: September 25, 2019
• First Posted: October 10, 2019
• Study Start: September 12, 2019
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: June 25, 2025

Record last verified: 2025-06

Locations

DE (6)