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GlioblastomaEarly Phase 1NCT04656535

AB154 Combined With AB122 for Recurrent Glioblastoma

A Early Phase 1 study testing Zimberelimab and Domvanalimab in people with Glioblastoma, run by Yale University at 3 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma
What is being tested?
Zimberelimab and Domvanalimab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
46 participants
Where
3 sitesUnited States
Study dates
21 Apr 2021to 31 Dec 2026
Phase
Early Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • First or second recurrence after treatment. Prior treatment must include at least radiation therapy.
  • Measurable contrast enhancing tumor by Response Assessment in Neuro-Oncology (RANO) criteria. Not required for post-surgery eligibility for treatment in cohort B.
  • Age ≥18 years.
  • Karnofsky performance status ≥80 (≥ 70 for eligibility for treatment after surgery in cohort B).
  • Patients must have adequate organ and marrow function as defined below within 14 days of treatment
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  • 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
  • Serum total bilirubin ≤ 1.5 X ULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
  • aspartate aminotransferase (SGOT) and alanine transaminase (SGPT) ≤ 2.5 X ULN
  • Albumin >2.5 mg/dL
  • International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • An interval of >=12 weeks from the end of prior radiation therapy is required unless there is either: i) histopathologic confirmation of recurrent tumor, or ii) new enhancement on MRI outside of the radiation treatment field.
  • An interval of >=4 weeks or 5 half-lives (whichever is shorter) after the last administration of any investigational agent or any other treatment prior to first study dose.
  • Female subjects of childbearing potential should have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Female subjects of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  • Ability to understand and the willingness to sign a written informed consent document.
  • ADDITIONAL CRITERIA FOR COHORT B
  • Deemed a candidate for tumor debulking, as determined by the neurosurgeon.

Who cannot join

  • 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.
  • Patients who have not recovered from adverse events due to prior therapy (i.e. >Grade 1) with the exception of alopecia and fatigue.
  • Patients with multifocal disease. (Cohort B only)
  • 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.
  • Patients receiving previous or current treatment with an immune checkpoint inhibitor.
  • Patients with a known diagnosis of immunodeficiency, including Human Immunodeficiency Virus (HIV) or acquired immunodeficiency syndrome (AIDS).
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  • Has known active Hepatitis B (e.g., Hepatitis B surface antigen reactive) or Hepatitis C (e.g., Hepatitis C Virus RNA [qualitative] is detected)
  • Has a known history of active tuberculosis (Bacillus Tuberculosis).
  • 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.
  • 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.
  • Has known history of, or any evidence of active, non-infectious pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Unable to undergo MRI of the brain with and without contrast enhancement (i.e. pacemaker, allergy to MRI contrast agent or any other contraindication for MRIs).
  • Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Yale University

    New Haven, Connecticut, 06519

  • University of California San Francisco

    San Francisco, California, 94143

Other trials in United States

About this study

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

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.

Read the 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.

Conditions
Glioblastoma
Being tested
Zimberelimab, Domvanalimab, Placebo
Keywords
Glioblastoma, Recurrent, PD1, TIGIT, Immunotherapy
Medical subject headings
Glioblastoma, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZimberelimabDrug

    Zimberelimab (AB122) is a fully human immunoglobulin G4 (hIgG4) monoclonal antibody (mAb) that targets PD-1.

  • DomvanalimabDrug

    Domvanalimab (AB 154) is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that targets TIGIT.

  • PlaceboDrug

    Saline placebo comparator for pre-surgery treatment in cohort B4

Study groups in NCT04656535
Study groupRoleWhat they receive
Zimberelimab (AB 122) + Domvanalimab (AB 154) Safety Cohort (Cohort A)ExperimentalEligible patients will be sequentially enrolled to receive intravenous domvanalimab (AB 154) combined with zimberelimab (AB 122) (N=6). domvanalimab (AB 154) will be given at a dose of 10 mg/kg and zimberelimab (AB 122) will be given at a dose of 240 mg (flat).
Receives: Drug: Zimberelimab; Drug: Domvanalimab
Domvanalimab (AB 154) Surgical Cohort (Cohort B1)ExperimentalCandidates for surgical resection will be enrolled and initiate study treatment approximately two weeks prior to the resection. The pre-surgical dose (neoadjuvant treatment) will be double-blinded. B1 (N=10): domvanalimab (AB 154) single agent (10 mg/kg) + placebo Following surgery, all patients will initiate treatment with the combination of domvanalimab (AB 154) and zimberelimab (AB 122). Domvanalimab (AB 154) will be given at a dose of 10 mg/kg and zimberelimab (AB 122) will be given at a dose of 240 mg (flat).
Receives: Drug: Domvanalimab; Drug: Placebo
Zimberelimab (AB 122) Surgical Cohort (Cohort B2)ExperimentalCandidates for surgical resection will be enrolled and initiate study treatment approximately two weeks prior to the resection. The pre-surgical dose (neoadjuvant treatment) will be double-blinded. B2 (N=10): zimberelimab (AB 122) single agent (240 mg) + placebo Following surgery, all patients will initiate treatment with the combination of domvanalimab (AB 154) and zimberelimab (AB 122). Domvanalimab (AB 154) will be given at a dose of 10 mg/kg and zimberelimab (AB 122) will be given at a dose of 240 mg (flat).
Receives: Drug: Zimberelimab; Drug: Placebo
Domvanalimab (AB 154) + Zimberelimab (AB 122) Surgical Cohort (Cohort B3)ExperimentalCandidates for surgical resection will be enrolled and initiate study treatment approximately two weeks prior to the resection. The pre-surgical dose (neoadjuvant treatment) will be double-blinded. B3 (N=10): domvanalimab (AB 154, 10 mg/kg) + zimberelimab (AB 122, 240 mg) Following surgery, all patients will initiate treatment with the combination of domvanalimab (AB 154) and zimberelimab (AB 122). Domvanalimab (AB 154) will be given at a dose of 10 mg/kg and zimberelimab (AB 122) will be given at a dose of 240 mg (flat).
Receives: Drug: Zimberelimab; Drug: Domvanalimab
Placebo Surgical Cohort (Cohort B4)ExperimentalCandidates for surgical resection will be enrolled and initiate study treatment approximately two weeks prior to the resection. The pre-surgical dose (neoadjuvant treatment) will be double-blinded. B4 (N=10): Two placebo infusions Following surgery, all patients will initiate treatment with the combination of domvanalimab (AB 154) and zimberelimab (AB 122). Domvanalimab (AB 154) will be given at a dose of 10 mg/kg and zimberelimab (AB 122) will be given at a dose of 240 mg (flat).
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] associated with the combination AB122 and AB154 in patients with recurrent glioblastoma

    Adverse events will be listed individually by patient and treatment group. The number of patients experiencing each adverse event will be summarized by organ and grade. The number and percentage of patients with adverse events in the different categories will be summarized by treatment group.

    Measured: through study completion, an average of 2 years

Secondary outcomes (2)

  1. Single cell RNA sequencing of tumor and blood after exposure to AB154 with and without AB122

    Pharmacodynamic effects of each pre-surgery treatment will be evaluated with single-cell RNA sequencing of tumor and blood to determine effects of each intervention on the immune response.

    Measured: through study completion, an average of 2 years

  2. Tregs and CD8 T cells ratio by immunofluorescence

    Resected tumors in cohorts B1 to 4 will be analyzed utilizing immunofluorescence for the ratio between Tregs and CD8 T cells, calculated by counting cells that are positive for a FoxP3 or a CD8 staining.

    Measured: through study completion, an average of 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Dec 2020
  2. Study start21 Apr 2021
  3. Primary completion17 Mar 2026
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
After the initial safety cohort confirms the safety of the dosing schedule an expansion surgical cohort will be enrolled and this cohort will be randomized to one of four treatment arms for the first cycle prior to surgery,
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
46 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04656535
Sponsor's protocol ID
2000028799
Other IDs
R01CA266757
Status last verified
Apr 2026
First submitted
18 Nov 2020
Last updated
17 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Zimberelimab and Domvanalimab in people with Glioblastoma, run by Yale University at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 17 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] associated with the combination AB122 and AB154 in patients with recurrent glioblastoma (time frame: through study completion, an average of 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04656535.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2026.

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