Olaptesed pegol for Glioblastoma

Inclusion criteria

• {"criterion_text":"- Dose Escalation Cohorts:\n- 3.\tPatient agreement to diagnostic and scientific work-up of glioblastoma tissue obtained during the preceding surgery or biopsy (e.g., MGMT promoter analysis, cytogenetic markers such as IDH-1 mutations, etc.)\n- 4.\tPatient agrees to subcutaneous port implantation\n- 9.\tEstimated minimum life expectancy 3 months\n- 5.\tNewly diagnosed, histologically confirmed, supratentorial WHO grade IV glioblastoma\n- 6.\ta) Status post biopsy or incomplete (detectable residual tumor as per postoperative T1-weighted, contrast-enhanced MRI scan) or complete resection (Arm A) OR b) Status post complete resection (Arm B) OR c) Status post complete or incomplete resection (circumscribed enhancing tumor ≤ 5.0 cm in largest diameter as per postoperative T1-weighted, contrast-enhanced MRI scan) (Arm C)\n- 7.\tUnmethylated MGMT promoter status\n- 8.\tMaximum Eastern Cooperative Oncology Group (ECOG) score 2\n- 9.\tEstimated minimum life expectancy 3 months\n- 10.\tStable or decreasing dose of corticosteroids during the week prior to inclusion\n- 11.\tThe following laboratory parameters should be within the ranges specified: •\tTotal bilirubin ≤ 1.5 x upper limit normal (ULN) •\tCreatinine ≤ 1.5 x ULN or glomerular filtration rate ≥ 60 mL/min/1.73m² •\tALT (alanine transaminase) ≤ 3 x ULN •\tAST (aspartate transaminase) ≤ 3 x ULN\n- 4.\tPatient agrees to subcutaneous port implantation\n- 12.\tFemale 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 (6 months Arm A, 4 months Arm C) following last dose of drug (more frequent pregnancy tests may be conducted if required per local regulations)\n- 13.\tMale patients must use an effective barrier method of contraception during study and for 3 months (6 months Arm A, 4 months Arm C) following the last dose if sexually active with a FCBP\n- 10.\tStable or decreasing dose of corticosteroids during the week prior to inclusion\n- 11.\tThe following laboratory parameters should be within the ranges specified: •\tTotal bilirubin ≤ 1.5 x upper limit normal (ULN) •\tCreatinine ≤ 1.5 x ULN or glomerular filtration rate ≥ 60 mL/min/1.73m² •\tALT (alanine transaminase) ≤ 3 x ULN •\tAST (aspartate transaminase) ≤ 3 x ULN\n- 12.\t 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)\n- 13.\tMale patients must use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with a FCBP\n- 1.\tWritten informed consent\n- 2.\tAge ≥18 years\n- 3.\tPatient agreement to diagnostic and scientific work-up of glioblastoma tissue obtained during the preceding surgery or biopsy (e.g., MGMT promoter analysis, cytogenetic markers such as IDH-1 mutations, etc.)\n- Expansion Group Arms D-H:\n- 1. Written informed consent\n- 2. Age ≥ 18 years\n- 3. Patient agreement to diagnostic and scientific work-up of glioblastoma tissue obtained during the preceding surgery (e.g., MGMT promoter analysis, cytogenetic markers such as IDH-1 mutations, etc.)\n- 4. Patient agrees to subcutaneous port implantation\n- 5. Newly diagnosed, histologically confirmed, supratentorial WHO grade 4 glioblastoma, IDH-wildtype according to the 2021 World Health Organization Criteria for CNS tumors\n- 6. Status post incomplete resection (detectable residual tumor as per postoperative T1-weighted, contrast-enhanced MRI scan)\n- 7. Unmethylated MGMT promoter status\n- 8. Maximum Eastern Cooperative Oncology Group (ECOG) score 2\n- 9. Estimated minimum life expectancy 3 months\n- 10. Stable or decreasing dose of corticosteroids during the week prior to inclusion\n- 11. The following laboratory parameters should be within the ranges specified: • Total bilirubin ≤ 1.5 x upper limit normal (ULN) • Body surface area (BSA) adjusted glomerular filtration rate (GFR) ≥ 60 mL/min (BSA-adjusted eGFR CKD-EPI (mL/min) = [eGFR CKD-EPI (mL/min/1.73 m²) x BSA (m²)]/ 1.73; BSA calculated by Du Bois formula) • Alanine transaminase (ALT) ≤ 3 x ULN • Aspartate transaminase (AST) ≤ 3 x ULN • Absolute neutrophil count (ANC) ≥ 1.5 x 10E9/L and platelet count ≥ 100 x 10E9/L\n- 12. Female patients of child-bearing potential (FCBP) 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 6 months following last dose of drug (more frequent pregnancy tests may be conducted if required per local regulations)\n- 13. Male patients must use an effective barrier method of contraception during study and for 6 months following the last dose if sexually active with a FCBP\n- 5. Newly diagnosed, histologically confirmed, supratentorial WHO grade 4 glioblastoma, IDH-wildtype according to the 2021 World Health Organization Criteria for CNS tumors\n- 6. Status post biopsy or incomplete resection (detectable residual tumor as per postoperative T1-weighted, contrast-enhanced MRI scan)\n- 7. Unmethylated MGMT promoter status\n- 8. Maximum Eastern Cooperative Oncology Group (ECOG) score 2\n- 1. Written informed consent\n- 2. Age ≥ 18 years"}

Exclusion criteria

• {"criterion_text":"- Dose Escalation Cohorts:\n- 10.\tAny other previous or concomitant experimental glioblastoma treatments\n- 11.\tPlacement of Gliadel® wafer, seeds, or ferromagnetic nanoparticles\n- 9.\tPlacement of Gliadel® wafer, seeds, or ferromagnetic nanoparticles\n- 12.\tPatients with a history of arterial or venous thrombosis (or any other disease) requiring permanent intake of anticoagulants (Arm A only)\n- 13.\tPregnancy or lactation\n- 14.\tUncontrolled intercurrent illness including, but not limited to ongoing or active infection, chronic liver disease (e.g., cirrhosis, hepatitis), diabetes mellitus, or subjects with either of the following: fasting blood glucose (FBG defined as fasting for at least 8 hours) ≥ 200 mg/dL (7.0 mmol/L), or HbA1c ≥ 8%, chronic renal disease, pancreatitis, chronic pulmonary disease, auto-immune diseases or psychiatric illness/social situations that would limit compliance with study requirements. 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.\n- 2.\tParticipation 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\n- 15.\tProlongation of coagulation factors ≥ 2.5 x ULN (Arm A only)\n- 16.\tTreatment not initiated within 6 weeks after first biopsy or surgery of glioblastoma\n- 17.\tPrior enrolment into this study\n- 2.\tContra-indication or known hypersensitivity to MRI contrast agents, bevacizumab (Arm A only), olaptesed pegol or polyethylene glycol\n- Expansion Group Arm C:\n- 2.\tParticipation 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\n- 3.\tContra-indication or known hypersensitivity to MRI contrast agents olaptesed pegol or polyethylene glycol or pembrolizumab (≥ Grade 3)\n- 10.\tPregnancy or lactation\n- 4.\tBiopsy-only of GBM with less than 20% of tumor removed\n- 5.\tPresence of extracranial metastatic or leptomeningeal disease\n- 6.\tSevere hypersensitivity (≥ Grade 3) to other monoclonal antibodies\n- 7.\tReceiving immunosuppressive therapy\n- 3.\tContra-indication or known hypersensitivity to MRI contrast agents, olaptesed pegol or polyethylene glycol\n- 8.\tPrevious or current treatment with an anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PDL2 agent\n- 4.\tPlanned hypofractionated radiotherapy\n- 9.\tPlanned hypofractionated radiotherapy\n- 10.\tCytostatic therapy (chemotherapy) within the past 5 years\n- 11.\tHistory of other cancers or secondary malignancy which is currently active (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)\n- 12.\tClinically significant or uncontrolled cardiovascular disease, including •\tMyocardial infarction in the previous 12 months •\tUncontrolled angina •\tCongestive heart failure (New York Heart Association functional classification of ≥2) •\tDiagnosed or suspected congenital long QT syndrome •\tQTc prolongation on an electrocardiogram prior to entry (>470 ms) •\tUncontrolled hypertension (blood pressure ≥ 160/95 mmHg) •\tHeart rate <50/min on the baseline electrocardiogram •\tHistory of ventricular arrhythmias of any clinically significant type (such as ventricular tachycardia, ventricular fibrillation or torsades de pointes) •\tCerebrovascular accident\n- 11.\tUncontrolled intercurrent illness including, but not limited to ongoing or active infection, chronic liver disease (e.g., cirrhosis, hepatitis), diabetes mellitus, or subjects with either of the following: fasting blood glucose (FBG defined as fasting for at least 8 hours) ≥ 200 mg/dL (7.0 mmol/L), or HbA1c ≥ 8%, chronic renal disease, pancreatitis, chronic pulmonary disease, or psychiatric illness/social situations that would limit compliance with study requirements. 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\n- 13.\tPrior radiotherapy to the head\n- 14.\tEvidence of acute intracranial / intra-tumoral hemorrhage\n- 15.\tAny other previous or concomitant experimental glioblastoma treatments\n- 16.\tPlacement of Gliadel® wafer, seeds, or ferromagnetic nanoparticles\n- 17.\tPregnancy or lactation\n- 1.\tInability to understand and collaborate throughout the study or inability or unwillingness to comply with study requirements\n- 4.\tCytostatic therapy (chemotherapy) within the past 5 years\n- 18.\tUncontrolled intercurrent illness including, but not limited to ongoing or active infection, chronic liver disease (e.g., cirrhosis, hepatitis), diabetes mellitus, or subjects with either of the following: fasting blood glucose (FBG defined as fasting for at least 8 hours) ≥ 200 mg/dL (7.0 mmol/L), or HbA1c ≥ 8%, chronic renal disease, pancreatitis, chronic pulmonary disease, auto-immune diseases or psychiatric illness/social situations that would limit compliance with study requirements. 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.\n- 19.\tReceived a live vaccine within 30 days prior to the first dose of study drug.\n- 20.\tKnown active central nervous system (CNS) metastases and/or carcinomatous meningitis. Previously treated brain metastases may participate provided these remain stable\n- 21.\tKnown history of HIV infection, hepatitis B or hepatitis C infection\n- 12.\tTreatment not initiated within 6 weeks after first biopsy or surgery of glioblastoma\n- 22.\tActive autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs)\n- 23.\tHistory of (non-infectious) pneumonitis / interstitial lung disease that required steroids or current pneumonitis / interstitial lung disease\n- 24.\tImmunodeficiency diagnosis or receiving chronic systemic steroid therapy (exceeding 10 mg daily of prednisone) or any other form of immunosuppressive therapy\n- 25.\tHigh dose of corticosteroids (> 4mg/day of dexamethasone or equivalent for at least 3 consecutive days) within two weeks prior to the first dose of study drug\n- 5.\tCytostatic therapy (chemotherapy) within the past 5 years\n- 26.\tTreatment not initiated within 6 weeks after first biopsy or surgery of glioblastoma\n- 27.\tPrior enrolment into this study\n- 5.\tHistory 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)\n- 6.\tClinically significant or uncontrolled cardiovascular disease, including •\tMyocardial infarction in the previous 12 months •\tUncontrolled angina •\tCongestive heart failure (New York Heart Association functional classification of ≥2) •\tDiagnosed or suspected congenital long QT syndrome •\tQTc prolongation on an electrocardiogram prior to entry (>470 ms) •\tUncontrolled hypertension (blood pressure ≥ 160/95 mmHg) •\tHeart rate <50/min on the baseline electrocardiogram •\tHistory of ventricular arrhythmias of any clinically significant type (such as ventricular tachycardia, ventricular fibrillation or torsades de pointes)\n- 7.\tPrior radiotherapy to the head\n- 8.\tAny other previous or concomitant experimental glioblastoma treatments\n- 13.\tPrior enrolment into this study\n- Expansion Group Arms D-H:\n- 1. Patients with tumors harboring IDH mutations\n- 2. Inability to understand and collaborate throughout the study or inability or unwillingness to comply with study requirements\n- 3. Participation in any clinical research study with administration of an investigational drug or therapy within 30 days prior to screening visit or observation period of competing studies\n- 4. Contra-indication or known hypersensitivity to MRI contrast agents, bevacizumab, olaptesed pegol or polyethylene glycol\n- 5. Planned hypofractionated radiotherapy\n- 6. Chemotherapy (cytotoxic/cytostatic) within the past 5 years\n- 7. 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)\n- 8. Secondary malignancy which is currently active\n- Expansion Group Arms A and B:\n- 1.\tInability to understand and collaborate throughout the study or inability or unwillingness to comply with study requirements\n- 2.\tParticipation 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\n- 7.\tSecondary malignancy which is currently active\n- 8.\tClinically significant or uncontrolled cardiovascular disease, including •\tMyocardial infarction in the previous 12 months •\tUncontrolled angina •\tCongestive heart failure (New York Heart Association functional classification of ≥2) •\tDiagnosed or suspected congenital long QT syndrome •\tQTc prolongation on an electrocardiogram prior to entry (>470 ms) •\tUncontrolled hypertension (blood pressure ≥ 160/95 mmHg) •\tHeart rate <50/min on the baseline electrocardiogram •\tHistory of ventricular arrhythmias of any clinically significant type (such as ventricular tachycardia, ventricular fibrillation or torsades de pointes) •\tCerebrovascular accident\n- 9.\tPrior radiotherapy to the head"}

Primary endpoints

• {"endpoint_text":"- \tSafety (adverse events)","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- Dose Escalation Cohorts und Expansion Group Arms A-C:","definition_or_measurement_approach":""}
• {"endpoint_text":"- • PFS at 6 months (PFS-6)","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Median progression-free survival (mPFS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Median overall survival (mOS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Tumor vascularization as per vascular MRI scans at baseline and 2, 4, and 6 months","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Topography of recurrence","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Determination of maximum tolerated dose (MTD)","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Definition of recommended Phase 2 dose (RP2D)","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Olaptesed plasma levels at steady state","definition_or_measurement_approach":""}
• {"endpoint_text":"- • NANO assessment","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Quality of Life","definition_or_measurement_approach":""}
• {"endpoint_text":"- Expansion Group Arms D-H:","definition_or_measurement_approach":""}
• {"endpoint_text":"- • PFS at 6 months (PFS-6)","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Median progression-free survival (mPFS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Median overall survival (mOS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Landmark overall survival at 18 months (OS18)","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Overall response rate (ORR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Olaptesed plasma levels at steady state","definition_or_measurement_approach":""}
• {"endpoint_text":"- • Quality of Life","definition_or_measurement_approach":""}

Germany

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

11-02-2026

Processing Time Days

694

Number Of Sites

6

Number Of Participants

136

Primary sponsor

Full Name

TME Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Contract research organisations

Name

FGK Clinical Research GmbH

Responsibilities

Codes: 1,10,12,6,7,9 (as listed in sponsor third party duties)

Third parties

• {"country":"Germany","full_name":"Axolabs GmbH","duties_or_roles":"Analysis of NOX-A12 from plasma samples","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Medizone Germany GmbH","duties_or_roles":"MVASI supply","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"spm2- safety projects and more GmbH","duties_or_roles":"","organisation_type":"Health care"}
• {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"Keytruda supply","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"FGK Clinical Research GmbH","duties_or_roles":"Responsibilities codes: 1,10,12,6,7,9","organisation_type":"Pharmaceutical company"}