RECRUITING

A Phase I/II Study of IVONESCIMAB in Recurrent Glioblastoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The goal of Phase 1 of this clinical research study is to find the highest tolerable dose and the recommended Phase 2 dose of ivonescimab that can be given to patients who have recurrent glioblastoma. The goal of Phase 2 of this clinical research study is to learn if the recommended Phase 2 dose of ivonescimab found in Phase 1 can help to control the disease.

Official Title

A Phase I/II Study of IVONESCIMAB in Recurrent Glioblastoma

Quick Facts

Study Start:2025-04-01

Study Completion:2030-01-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06672575

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Age ≥18 years 2. Karnofsky Performance Status (KPS) of 60 or greater 3. Recurrent supratentorial Glioblastoma that has progressed following standard therapy; patients must have previously been treated with radiation with or without temozolomide. 1. Patients will be eligible at first or second recurrence. 2. Patients must be greater than 12 weeks from completion of initial chemoradiation at the time of progression, with the exception that patients with biopsy-confirmed recurrent disease prior to this time window can be enrolled. 4. Diagnosis of Glioblastoma IDH-wildtype, WHO Grade 4 consistent with WHO CNS 2021 criteria. This will include patients with a diagnosis of molecular glioblastoma. 5. Measurable or evaluable disease per RANO criteria 6. A baseline MRI Brain no more than 14 days prior to study enrollment 7. Adequate Organ Function, with screening labs performed within 14 days of treatment initiation: * 1.5 × ULN, and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless abnormalities are unrelated to coagulopathy or prophylactic coagulation) 8. Female patients of childbearing age must have negative serum pregnancy test results before randomization or per region-specific guidance documented in the informed consent and a negative urine pregnancy test on the day of first dose prior to dosing. 9. Female patient of childbearing potential having sex with an unsterilized male partner must agree to use a highly effective method of contraception from the beginning of screening until 120 days after the last dose of the ivonescimab. 10. Male patients of childbearing potential having sex with a female partner of childbearing potential must agree to use an effective method of contraception from the beginning of screening until Day 120 after the last dose of ivonescimab. 11. Ability to understand and willingness to sign informed consent form prior to the initiation of study and any study procedures. 1. Participants with cognitive impairment may be enrolled. The formal consent for such participants will be obtained from their legally authorized representative. However, participants will be informed about the research to the maximum extent compatible with their understanding. Assent will be obtained from such participants who will sign and date the consent form if capable. 2. Non-English speakers are allowed to enroll provided consent and all visits will be conducted with a medical interpreter.	1. Major surgical procedures or serious trauma, or plans for major surgical procedures within 4 weeks after the first dose (as determined by the investigator). 2. Currently pregnant or breastfeeding. 3. History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms, including but not limited to: 1. Note: Patients with clinically asymptomatic presence of hemosiderin, resolving postoperative changes or punctate intratumoral hemorrhage are permitted 2. Gastrointestinal bleeding 4. Current hypertension with systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy 5. Is receiving dexamethasone \>2mg daily, or the corticosteroid equivalent thereof. 6. History of major diseases, specifically: 1. Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association \[NYHA\] classification ≥ grade 2) or vascular disease (eg, aortic aneurysm at risk of rupture), or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia) 2. History of esophageal gastric varices, severe ulcers, wounds that do not heal, abdominal fistula, intra-abdominal abscesses, or acute gastrointestinal bleeding 3. History of arterial thromboembolic event, venous thromboembolic event of Grade 3 and above as specified in National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy 4. Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks beforerandomization 5. History of perforation of the gastrointestinal tract and/or fistula, history of gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection) 7. History of other malignancy diagnosed or requiring treatment within the past 3 years prior to enrolment, with the exception of those with negligible expected risk of metastasis or death (including adequately treated non- melanoma skin cancer or cervical carcinoma in situ). 8. History of prior treatment of GB with anti-VEGF and/or anti-PD-1/PDL-1 agents, including monotherapy with either category or combinations thereof. 9. Has received prior interstitial brachytherapy, interstitial thermal therapy, implanted chemotherapy, or therapeutics delivered by local injection or convection enhanced deliver. Prior treatment with Gliadel ® wafers will be excluded. Concurrent use of devices such as Tumor Treating Fields is not permitted. 10. Has known leptomeningeal disease, gliomatosis cerebri, extracranial disease, or multicentric disease (regionally multifocal enhancing disease with continguous T2/FLAIR is permitted to be enrolled) 11. Uncontrolled seizures after best medical therapy or other neurological conditions including clinically significant autoimmune neurological disorders which can increase risk for adverse effects or confound assessment of study outcomes as determined by the treating physician and PI 12. History of clinically significant autoimmune disease including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, granulomatosis with polyangiitis, Sjogren's syndrome, GuillainBarré syndrome, multiple sclerosis, vasculitis or glomerulonephritis 1. Patients with a history of autoimmune hypothyroidism may be eligible if on a stable dose of thyroid replacement hormone 2. Patients with controlled Type 1 diabetes mellitus may be eligible if on a stable insulin regimen 3. Patients with dermatologic disorders (e.g., eczema) may be eligible if well controlled at baseline and not requiring systemic treatment or other treatments beyond low potency topical steroids 13. Has contraindication for undergoing MRI scans or receiving MRI contrast. 14. History of stroke or TIA within 6 months prior to study enrolment. 15. Imaging during the screening period shows that the patient has: 1. Radiologically documented evidence of major blood vessel invasion or encasement by cancer 2. Radiographic evidence of intratumor cavitation

Inclusion Criteria

Exclusion Criteria

1. Age ≥18 years
2. Karnofsky Performance Status (KPS) of 60 or greater
3. Recurrent supratentorial Glioblastoma that has progressed following standard therapy; patients must have previously been treated with radiation with or without temozolomide.
1. Patients will be eligible at first or second recurrence.
2. Patients must be greater than 12 weeks from completion of initial chemoradiation at the time of progression, with the exception that patients with biopsy-confirmed recurrent disease prior to this time window can be enrolled.
4. Diagnosis of Glioblastoma IDH-wildtype, WHO Grade 4 consistent with WHO CNS 2021 criteria. This will include patients with a diagnosis of molecular glioblastoma.
5. Measurable or evaluable disease per RANO criteria
6. A baseline MRI Brain no more than 14 days prior to study enrollment
7. Adequate Organ Function, with screening labs performed within 14 days of treatment initiation:
* 1.5 × ULN, and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless abnormalities are unrelated to coagulopathy or prophylactic coagulation)
8. Female patients of childbearing age must have negative serum pregnancy test results before randomization or per region-specific guidance documented in the informed consent and a negative urine pregnancy test on the day of first dose prior to dosing.
9. Female patient of childbearing potential having sex with an unsterilized male partner must agree to use a highly effective method of contraception from the beginning of screening until 120 days after the last dose of the ivonescimab.
10. Male patients of childbearing potential having sex with a female partner of childbearing potential must agree to use an effective method of contraception from the beginning of screening until Day 120 after the last dose of ivonescimab.
11. Ability to understand and willingness to sign informed consent form prior to the initiation of study and any study procedures.
1. Participants with cognitive impairment may be enrolled. The formal consent for such participants will be obtained from their legally authorized representative. However, participants will be informed about the research to the maximum extent compatible with their understanding. Assent will be obtained from such participants who will sign and date the consent form if capable.
2. Non-English speakers are allowed to enroll provided consent and all visits will be conducted with a medical interpreter.

1. Major surgical procedures or serious trauma, or plans for major surgical procedures within 4 weeks after the first dose (as determined by the investigator).
2. Currently pregnant or breastfeeding.
3. History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms, including but not limited to:
1. Note: Patients with clinically asymptomatic presence of hemosiderin, resolving postoperative changes or punctate intratumoral hemorrhage are permitted
2. Gastrointestinal bleeding
4. Current hypertension with systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy
5. Is receiving dexamethasone \>2mg daily, or the corticosteroid equivalent thereof.
6. History of major diseases, specifically:
1. Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association \[NYHA\] classification ≥ grade 2) or vascular disease (eg, aortic aneurysm at risk of rupture), or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia)
2. History of esophageal gastric varices, severe ulcers, wounds that do not heal, abdominal fistula, intra-abdominal abscesses, or acute gastrointestinal bleeding
3. History of arterial thromboembolic event, venous thromboembolic event of Grade 3 and above as specified in National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy
4. Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks beforerandomization
5. History of perforation of the gastrointestinal tract and/or fistula, history of gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection)
7. History of other malignancy diagnosed or requiring treatment within the past 3 years prior to enrolment, with the exception of those with negligible expected risk of metastasis or death (including adequately treated non- melanoma skin cancer or cervical carcinoma in situ).
8. History of prior treatment of GB with anti-VEGF and/or anti-PD-1/PDL-1 agents, including monotherapy with either category or combinations thereof.
9. Has received prior interstitial brachytherapy, interstitial thermal therapy, implanted chemotherapy, or therapeutics delivered by local injection or convection enhanced deliver. Prior treatment with Gliadel ® wafers will be excluded. Concurrent use of devices such as Tumor Treating Fields is not permitted.
10. Has known leptomeningeal disease, gliomatosis cerebri, extracranial disease, or multicentric disease (regionally multifocal enhancing disease with continguous T2/FLAIR is permitted to be enrolled)
11. Uncontrolled seizures after best medical therapy or other neurological conditions including clinically significant autoimmune neurological disorders which can increase risk for adverse effects or confound assessment of study outcomes as determined by the treating physician and PI
12. History of clinically significant autoimmune disease including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, granulomatosis with polyangiitis, Sjogren's syndrome, GuillainBarré syndrome, multiple sclerosis, vasculitis or glomerulonephritis
1. Patients with a history of autoimmune hypothyroidism may be eligible if on a stable dose of thyroid replacement hormone
2. Patients with controlled Type 1 diabetes mellitus may be eligible if on a stable insulin regimen
3. Patients with dermatologic disorders (e.g., eczema) may be eligible if well controlled at baseline and not requiring systemic treatment or other treatments beyond low potency topical steroids
13. Has contraindication for undergoing MRI scans or receiving MRI contrast.
14. History of stroke or TIA within 6 months prior to study enrolment.
15. Imaging during the screening period shows that the patient has:
1. Radiologically documented evidence of major blood vessel invasion or encasement by cancer
2. Radiographic evidence of intratumor cavitation

Contacts and Locations

Study Contact

Evguenia Gachimova, MD

CONTACT

832-266-3519

Neuro-OncologyResearchTrials@mdanderson.org

Principal Investigator

Anuj D Patel, MD

PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Study Locations (Sites)

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030

United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: M.D. Anderson Cancer Center

Anuj D Patel, MD, PRINCIPAL_INVESTIGATOR, M.D. Anderson Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-04-01

Study Completion Date2030-01-31

Study Record Updates

Study Start Date2025-04-01

Study Completion Date2030-01-31

Terms related to this study

Additional Relevant MeSH Terms

Glioblastoma