A Trial of Pembrolizumab for Refractory Atypical and Anaplastic Meningioma

Inclusion Criteria

• •1. Be willing and able to provide written informed consent/assent for the trial.
• •2. Be 18 years of age on day of signing informed consent.
• •3. Have measurable disease based on RECIST 1.1.
• •4. Histologically, previously proven, grade II or III meningioma, HPC or classic radiographic features of a recurrent surgically inaccessible atypical or anaplastic meningioma.
• •5. All patients would have to have recurrence despite radiotherapy, unless radiotherapy is contraindicated.
• •6. No limit on the number of prior surgeries, radiation or radiosurgery treatments.
• •7. No limit on prior systemic therapies - chemotherapy or biological agents.
• •8. Patients who received stereotactic radiosurgery (SRS) are eligible without histologic documentation of recurrence if at least 6 months have passed from previous SRS treatment, and preferably, but not necessarily a 2-fluoro-2-deoxy-D-glucose PET imaging demonstrated hypermetabolism.
• •9. KPS≥50%
• •10. At least 4 weeks since any prior therapy.
• •11. Life expectancy of at least 4 months.
• •12. Dexamethasone use will be allowed up to a dose of 2mg per day. Steroids dose should be reduced or stopped 7 days prior to treatment with study drug.
• •13. Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
• •Table 1 Adequate Organ Function Laboratory Values
• •Hematological Absolute neutrophil count (ANC)≥1,500 /mcL Platelets≥100,000 / mcL Hemoglobin≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment) Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl)≤1.5 X upper limit of normal (ULN) OR
• •≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN Hepatic Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR
• •≤ 5 X ULN for subjects with liver metastases Albumin \>2.5 mg/dL Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT)
• •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
• •≤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 a Creatinine clearance should be calculated per institutional standard.
• •14. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• •15. Female subjects of childbearing potential (Section 5.7.2) must be willing to use an adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the course of the study through 120 days after the last dose of study medication.
• •Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• •16. Male subjects of childbearing potential (Section 5.7.1) must agree to use an adequate method of contraception as outlined in Section 5.7.1- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• •Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.