Avelumab and Stereotactic Body Radiation Therapy in Treating Patients with Malignant Mesothelioma

Inclusion Criteria

• Patient willing and able to provide written informed consent for the trial
• Histologically or cytologically confirmed malignant pleural or peritoneal mesothelioma (MPM)
• No plans for surgical resection
• At least one prior line of systemic therapy; Note: Patients on prior immunotherapy are eligible
• At least one targetable lesion appropriate for palliative SBRT and one non-target lesion
• Karnofsky performance score (KPS) >= 70%
• If of childbearing potential, must be willing to use highly effective mode of contraception for at least one month prior, during, and for 2 months after the end of active therapy
• Absolute neutrophil count >= 1.5 K/mcL
• Platelet count >= 100 K/mcL
• Adequate renal function as defined by an estimated creatinine clearance >= 30 mL/min according to the Cockcroft-Gault formula or serum creatinine =< 1.5 x upper limit of normal (ULN)
• Hemoglobin >= 9 g/dL (prior transfusion permitted)
• Total bilirubin level =< 1.5 x the upper limit of normal (ULN) range
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =< 2.5 x ULN or AST and ALT levels =< 5 x ULN (for subjects with documented metastatic disease to the liver)
• If the patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy

Exclusion Criteria

• Currently participating and receiving another study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
• Prior radiation therapy precluding SBRT
• Continuous oxygen use
• Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or equivalent; c. steroids as premedication for hypersensitivity reactions (e.g., computed tomography [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 diseases not requiring immunosuppressive treatment are eligible; replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
• Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v]4.03 grade >= 3)
• Patient who rapidly progressed on prior immunotherapy, as determined by the treating physician, are not eligible
• Prior Therapies: * Treatment with a monoclonal antibody within 4 weeks prior to study day 1 or has not recovered (i.e., >= grade 1 at baseline) from adverse events due to agents administered * Prior chemotherapy, targeted small molecule therapy, within 4 weeks prior to study day 1 or has not recovered (i.e., >= grade 1 at baseline) from adverse events due to a previously administered agent (excluding grade 2 neuropathy) * Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) within 4 weeks prior to study day 1 or has not recovered (i.e., >= grade 1 at baseline) from adverse events
• Comorbidities or prior conditions: * Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial * Prior organ transplantation including allogenic stem-cell transplantation * Known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy * Known history of active TB (Tuberculosis) * Known history of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome * Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening or positive serologies indicating prior infection * Active infection requiring systemic therapy * Evidence of interstitial lung disease or active, non-infectious pneumonitis * Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (>= New York Heart Association Classification class II), or serious cardiac arrhythmia requiring medication
• Pregnant women or women who are breastfeeding or of childbearing potential and not using a highly effective method of birth control for at least one month prior to enrollment; if the risk of contraception exists, male and female subjects must use highly effective contraception throughout the study and for at least 60 days after last avelumab treatment * Highly effective contraception includes either 2 barrier methods (diaphragm, condom by the partner, copper intrauterine device, sponge, or spermicide), or 1 barrier method and 1 hormonal method (any oral, subcutaneous, intrauterine, or intramuscular registered and marketed contraceptive agent that contains an estrogen and/or a progesterone agent)
• Vaccination within 4 weeks prior to the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
• Concomitant use of the following medications * Any investigational anticancer therapy * Any concurrent chemotherapy, immunotherapy, or biologic therapy; concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable * Immunosuppressive medications including, but not limited to systemic corticosteroids (> 10 mg/day prednisone or equivalent), methotrexate, azathioprine, and tumor necrosis factor alpha (TNF-alpha) blockers; use of immunosuppressive medications for the management of investigational product-related adverse event (AE)s, in subjects with contrast allergies is acceptable; in addition, use of inhaled and intranasal corticosteroids is permitted
• Known contraindications to radiotherapy