Single-arm Dose-escalation Phase 1/2 Study of Olaptesed Pegol (NOX-A12) in Combination With Irradiation in Inoperable or Partially Resected First-line Glioblastoma Patients With Unmethylated MGMT Promoter With a 3-arm Expansion Group Including Fully Resected Patients and Combination With Bevacizumab or Pembrolizumab
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 27
- Locations
- 5
- Primary Endpoint
- Safety - Number of patients with treatment-related adverse events as assessed by CTCAE
Study Overview
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, (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, (iii) olaptesed pegol in combination with radiation therapy in patients with newly diagnosed glioblastoma of unmethylated MGMT promoter status after complete tumor resection, and (iv) olaptesed pegol in combination with radiation therapy and pembrolizumab in patients with newly diagnosed glioblastoma of unmethylated MGMT promoter status after either complete or incomplete tumor resection.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
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
Intervention: Radiotherapy (Radiation)
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
Intervention: Radiotherapy (Radiation)
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
Intervention: Radiotherapy (Radiation)
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
Intervention: Radiotherapy (Radiation)
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
Intervention: Radiotherapy (Radiation)
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
Intervention: Radiotherapy (Radiation)
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
Intervention: Radiotherapy (Radiation)
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
Intervention: Radiotherapy (Radiation)
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
Intervention: Radiotherapy (Radiation)
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
Intervention: Radiotherapy (Radiation)
Expansion group, Arm H: Standard of care - Temozolomide + Radiotherapy
oral treatment up to 35 weeks according to current SPC
Intervention: Radiotherapy (Radiation)
Expansion group, Arm H: Standard of care - Temozolomide + Radiotherapy
oral treatment up to 35 weeks according to current SPC
Intervention: Temozolomide (TMZ) (Drug)
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
Intervention: Olaptesed pegol (Drug)
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
Intervention: Olaptesed pegol (Drug)
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
Intervention: Olaptesed pegol (Drug)
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
Intervention: Olaptesed pegol (Drug)
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
Intervention: Olaptesed pegol (Drug)
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
Intervention: Bevacizumab (Drug)
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
Intervention: Olaptesed pegol (Drug)
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
Intervention: Pembrolizumab (Drug)
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
Intervention: Olaptesed pegol (Drug)
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
Intervention: Bevacizumab (Drug)
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
Intervention: Olaptesed pegol (Drug)
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
Intervention: Olaptesed pegol (Drug)
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
Intervention: Bevacizumab (Drug)
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
Intervention: Bevacizumab (Drug)
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
Intervention: Olaptesed pegol (Drug)
Outcomes
Primary Outcomes
Safety - Number of patients with treatment-related adverse events as assessed by CTCAE
Time Frame: through study completion, an average of 3 years
Number of patients with treatment-related adverse events as assessed by CTCAE
Secondary Outcomes
- 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)
- Plasma level of olaptesed pegol(9 weeks after treatment start)
- Quality of Life (QoL) EORTC QLQ-C30 Module(through study completion, an average of 3 years)
- Quality of Life (QoL) EORTC QLQ BN-20 Module(through study completion, an average of 3 years)
- Efficacy - Tumor vascularization as per vascular MRI(through study completion, an average of 3 years)
- Neurologic functions as measured by the NANO scale(24 months)