Neoadjuvant Avelumab and Hypofractionated Proton Radiation Therapy Followed by Surgery for Recurrent Radiation-refractory Meningioma

Inclusion Criteria:

* Diagnosis of recurrent or progressive histologically confirmed WHO grade I-III meningioma which has failed maximal safe resection and radiation therapy.
* At least one prior surgery with available archival formalin-fixed paraffin-embedded (FFPE) tumor blocks. In the case that tumor block is unavailable, unstained tissue sections may be used in its place.
* Prior treatment must include external beam radiation, radiosurgery, or combination of both.
* Deemed eligible for additional partial resection by treating physician and determined to be safe to receive 3 months of neoadjuvant therapy before planned surgery.
* Age ≥ 18 years old. 6. Karnofsky performance status (KPS) ≥ 60.
* Adequate organ and bone marrow function (as defined by the following laboratory values):

  * Absolute neutrophil count ≥ 1.5 × 10⁹ cells per L
  * Platelet count ≥ 100 × 10⁹ platelets per L
  * Hemoglobin ≥ 9 g/dL but transfusion allowed
  * Total bilirubin concentration of ≤ 1.5 × the upper limit of normal \[ULN\] range
  * Aspartate aminotransferase and alanine aminotransferase concentrations of ≤ 2.5 × ULN)
  * Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula.
* Dexamethasone dose ≤ 4mg daily.
* Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in the study, she must inform her treating physician immediately.
* Able to understand and willing to sign an IRB approved written informed consent document (or legally authorized representative, if applicable)

Exclusion Criteria:

* Previous treatment with PD-1 or PD-L1 directed therapy.
* Active infection requiring systemic therapy.
* Uncontrolled intercurrent illness including, but not limited to, clinically significant (i.e. active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), congestive heart failure (≥ NYHA class II), unstable angina pectoris, or serious cardiac arrhythmia requiring medication.
* Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
* Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).
* Currently receiving any other investigational agents.
* Current use of immunosuppressive medication, EXCEPT for the following:

  * Intranasal, inhaled, topical steroids, or local steroid injection (e.g. intra-articular injection)
  * Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent
  * Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)
* Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
* Prior organ transplantation including allogeneic stem cell transplantation.
* Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis, or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
* Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines.
* History of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to avelumab or other agents used in the study (or monoclonal antibodies).
* Persisting toxicity related to prior therapy (CTCAE \> grade 1); however, alopecia, sensory neuropathy ≤ grade 2, or other ≤ grade 2 not constituting a safety risk based on the investigator's judgment are acceptable.
* Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.