AB154 Combined With AB122 for Recurrent Glioblastoma

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
• •* 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
• •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 \>=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.
• •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.