A Multi-Center Phase 0/I trial of anti-TIGIT antibody AB154 in combination with anti-PD1 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 AB154
combined with AB122 (N=6). AB154 will be given at a dose of 10 mg/kg and AB122 will be given
at a dose of 240 mg (flat).
Cohort B: Expansion surgical cohort. The purpose of cohort B is to provide an additional
safety evaluation of AB154 + AB122 as well as tissue and blood for exploratory ancillary
studies investigating the effects of AB154 + AB122 in the tumor and tumor microenvironment. A
total of 40 patients will be enrolled in this cohort.
1. Grade IV glioma (glioblastoma and its variants according to the World Health
Organization 2016), confirmed in tissue at time of initial diagnosis.
2. First or second recurrence after treatment. Prior treatment must include at least
3. Measurable contrast enhancing tumor by Response Assessment in Neuro-Oncology (RANO)
4. Age ≥18 years.
5. Karnofsky performance status ≥80
6. Patients must have adequate organ and marrow function as defined below within 14 days
- 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 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
7. 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.
8. An interval of >=3 weeks or 5 half-lives (whichever is longer) after the last
administration of any investigational agent or any other treatment prior to first
9. 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.
10. Ability to understand and the willingness to sign a written informed consent document.
ADDITIONAL CRITERIA FOR COHORT B
11. Deemed a candidate for tumor debulking, as determined by the neurosurgeon.
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.
11. Has known history of, or any evidence of active, non-infectious pneumonitis.
12. Has an active infection requiring systemic therapy.
13. 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.
14. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
15. 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.
16. 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).
17. 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.