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AB154 Combined With AB122 for Recurrent Glioblastoma | Clinical Trials | Clareo Health

ACTIVE_NOT_RECRUITINGEARLY_PHASE1

AB154 Combined With AB122 for Recurrent Glioblastoma

A Multi-Center Phase 0/I Trial of Anti-TIGIT Antibody AB154 in Combination With Anti-PD-1 Antibody AB122 for Recurrent Glioblastoma.

NCT04656535•Yale University

View on ClinicalTrials.gov

Summary

Detailed Description

This is a phase 0/I exploratory study. Patients at first or second recurrence of glioblastoma will be enrolled. The study will be divided into two cohorts: Cohort A (safety cohort) and Cohort B (surgical patient cohort). Cohort A: Eligible patients will be sequentially enrolled to receive intravenous domvanalimab combined with zimberelimab (N=6). Domvanalimab will be given at a dose of 10 mg/kg and zimberelimab will be given at a dose of 240 mg (flat). The dosing was determined in a separate study in solid tumors; this cohort will confirm the safety of the dosing schedule in patients with brain tumors. Cohort B: Expansion surgical cohort. The purpose of cohort B is to provide an additional safety evaluation of domvanalimab + zimberelimab as well as tissue and blood for exploratory ancillary studies investigating the effects of domvanalimab + zimberelimab in the tumor and tumor microenvironment. A total of 46 patients will be enrolled in this cohort. Following completion of cohort A, patients who are candidates for surgical resection for management of tumor progression (i.e. need for diagnostic confirmation or tumor debulking) will be enrolled prior to surgical resection, and initiate study treatment approximately two weeks prior to the resection. Patients will be randomized to one of the four treatment arms and initiate treatment prior to surgery, according to treatment assignment. The pre-surgical dose (neoadjuvant treatment) will be double-blinded, to minimize dropouts. A total of 10 patients will be allocated to each one of the following groups in a blinded fashion, approximately two weeks before surgery: * B1 (N=10): domvanalimab single agent (10 mg/kg) + placebo * B2 (N=10): zimberelimab single agent (240 mg) + placebo * B3 (N=10): domvanalimab (10 mg/kg) +zimberelimab (240 mg) * B4 (N=10): Two placebo infusions Two to six weeks, following surgery, all patients (N=46) will be re-screened and if still eligible will initiate treatment with the combination of domvanalimab and zimberelimab.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Grade IV glioma (glioblastoma and its variants according to the World Health Organization 2021), confirmed in tissue at time of initial diagnosis. Tumors with an IDH 1 or 2 mutation are excluded. Sequencing of IDH 1 and 2 is not required but, at a minimum, a negative result for the presence of IDH-1 R132H mutation on IHC is required for eligibility.
•2. First or second recurrence after treatment. Prior treatment must include at least radiation therapy.
•3. Measurable contrast enhancing tumor by Response Assessment in Neuro-Oncology (RANO) criteria. Not required for post-surgery eligibility for treatment in cohort B.
•4. Age ≥18 years.
•5. Karnofsky performance status ≥80 (≥ 70 for eligibility for treatment after surgery in cohort B).
•6. Patients must have adequate organ and marrow function as defined below within 14 days of treatment
•* Absolute neutrophil count (ANC) ≥1,500 /mcL
•* Platelets ≥100,000 / mcL
•* Hemoglobin ≥9 g/dL or ≥ 5.6 mmol/L without transfusion or Erythropoietin (EPO) dependency (within 7 days of assessment)
•* Serum creatinine ≤1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥ 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN
+11 more criteria

Exclusion Criteria

•1. Patients who have been treated with bevacizumab. Note: Previous use of intra-arterial bevacizumab may be allowed, contingent upon review and approval by study principal investigator and sponsor.
•2. Patients who have not recovered from adverse events due to prior therapy (i.e. \>Grade 1) with the exception of alopecia and fatigue.
•3. Patients with multifocal disease. (Cohort B only)
•4. Subjects requiring escalating or chronic supraphysiologic doses of corticosteroids (\> 10 mg/d of prednisone equivalent or \> 2 mg dexamethasone) for control of disease at the time of registration.
•5. Patients receiving previous or current treatment with an immune checkpoint inhibitor.
•6. Patients with a known diagnosis of immunodeficiency, including Human Immunodeficiency Virus (HIV) or acquired immunodeficiency syndrome (AIDS).
•7. Has known active Hepatitis B (e.g., Hepatitis B surface antigen reactive) or Hepatitis C (e.g., Hepatitis C Virus RNA \[qualitative\] is detected)
•8. Has a known history of active tuberculosis (Bacillus Tuberculosis).
•9. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
•10. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
+7 more criteria

Locations (3)

University of California San Francisco

San Francisco, California, United States

Yale University

New Haven, Connecticut, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Key Dates

Start Date

April 21, 2021

Primary Completion Date

July 30, 2026

Completion Date

December 31, 2026

Last Updated

January 7, 2026

Enrollment

ESTIMATED participants

Conditions

Glioblastoma

Interventions

Zimberelimab

DRUG

Domvanalimab

DRUG

Placebo

DRUG

Collection of Blood and Urine Samples in Patients Receiving Radiation Therapy for Glioblastoma Multiforme

NCT00083512

Glioblastoma Multiforme

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RECRUITINGPHASE1

Testing the Addition of an Anti-Cancer Drug, Triapine, to the Usual Radiation Therapy for Recurrent Glioblastoma or Astrocytoma

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Astrocytoma, IDH-Mutant, Grade 2Recurrent Adult Diffuse Hemispheric Glioma, H3 G34-Mutant+5 more

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: January 7, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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AB154 Combined With AB122 for Recurrent Glioblastoma

Inclusion Criteria

Exclusion Criteria

Collection of Blood and Urine Samples in Patients Receiving Radiation Therapy for Glioblastoma Multiforme

Testing the Addition of an Anti-Cancer Drug, Triapine, to the Usual Radiation Therapy for Recurrent Glioblastoma or Astrocytoma

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Study of TLX101-Tx Plus Standard of Care (SoC) Versus SoC Alone for the Treatment of Patients With Recurrent Glioblastoma