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

Sponsor
TME Pharma AG
Study ID
NCT04121455
Phase
PHASE1/PHASE2
Status
Active Not Recruiting

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Olaptesed pegol — DRUG
    Olaptesed pegol continuous i.v. administration
  • Radiotherapy — RADIATION
    Radiotherapy in weeks 1-6; cumulative dose of 60 Gy in 2 Gy fractions
  • Bevacizumab — DRUG
    Bevacizumab every 2 weeks i.v. infusion
  • Pembrolizumab — DRUG
    Pembrolizumab every 3 weeks i.v. for 26 weeks
  • Temozolomide (TMZ) — DRUG
    oral treatment according to current SPC

Study Details

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.

Key Dates

First listed
Oct 10, 2019
Start date
Sep 12, 2019
Status verified
Jun 2025
Primary completion
Dec 31, 2028
Completion
Dec 31, 2028

Study Design

Enrollment
117 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Cohort 1: 200 mg Olaptesed pegol + Radiotherapy
    olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6
  • Experimental: Cohort 2: 400 mg Olaptesed pegol + Radiotherapy
    olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6
  • Experimental: Cohort 3: 600 mg Olaptesed pegol + Radiotherapy
    olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6
  • Experimental: Expansion group, Arm A: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab
    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
  • Experimental: Expansion group, Arm B: 600 mg Olaptesed pegol + Radiotherapy
    olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6, completely resected patients
  • Experimental: Expansion group, Arm C: 600 mg Olaptesed pegol + Radiotherapy + 200 mg Pembrolizumab
    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
  • Experimental: Expansion group, Arm D: 200 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab
    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
  • Experimental: Expansion group, Arm E: 400 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab
    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
  • Experimental: Expansion group, Arm F: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kgBevacizumab
    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
  • Experimental: Expansion group, Arm G: 600 mg Olaptesed pegol + Radiotherapy
    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
  • Active Comparator: Expansion group, Arm H: Standard of care - Temozolomide + Radiotherapy
    oral treatment up to 35 weeks according to current SPC

Primary Outcome Measure

Safety - Number of patients with treatment-related adverse events as assessed by CTCAE [ Time Frame: through study completion, an average of 3 years ]

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