50 20.0 APPENDI CES .................................................................................................................... 51 Memorial Sloan Kettering Cancer Center IRB Number: 17- 358 A(7) Approval date: 25 -Feb-2022 Page 7 of 51 List of Abbreviations (alphabetical) ADCC Antibody -dependent cell-mediated cytotoxicity ADR Adverse drug reaction AE Adverse event ALT Alanine aminotransferase AST Aspartate aminotransferase CI Confidence interval CPK Creatine phosphokinase CR Complete response CTCAE Common Terminology Criteria for Adverse Events CTLA -4 Cytotoxic T-lymphocyte-associated protein 4 DCE DCE Dynamic contrast -enhanced DLT Dose -limiting toxicity DWI Diffusion -weighted imaging EOT End of treatment GGT Gamma -glutamyl transferase IRB Institutional Review Board irAE Immune -related adverse event KPS Karnofsky Performance Status mAb Monoclonal antibody MPM Malignant pleural/peritoneal mesothelioma MRI Magnetic resonance imaging ORR Overall response rate OS Overall survival PD Progression of disease PD-1 Programmed death 1 PD-L1 Programmed death ligand 1 PET Positron emission tomography PR Partial response Q2W Every other week RECIST Response Evaluation Criteria in Solid Tumors SBRT Stereotactic Body Radiotherapy SD Stable disease SPD Sum of the products of diameters TB Tuberculosis TCRs T-cell receptors TILs Tumor infiltrating lymphocytes ULN Upper limit of normal Memorial Sloan Kettering Cancer Center IRB Number: 17- 358 A(7) Approval date: 25 -Feb-2022 Page 8 of 51 1.0 PROTOCOL SUMMARY AND/OR SCHEMA Study Title A Safety Study of Avelumab plus SBRT in Malignant Mesothelioma (MPM) Investigational drug Avelumab Study Centers MSKCC Main Campus and Regional S i tes Study Objectives To evaluate the efficacy and safety (defined as the incidence of any grade 3+ non-hematologic toxicity) of combining SBRT and avelumab for the treatment of MPM Study Endpoints Primary Endpoint • Safety of avelumab + SBRT: rate of grade 3 or higher non- hematologic toxicity (CTCAE v4.0) Secondary Endpoint • • Overall response rate defined by modified RECIST 1.1 for mesothelioma • Response of irradiated (in-field) and unirradiated (out- of-field) lesions as defined by RECIST 1.1 • Progression- free and overall survival Exploratory Objectives • T-cell infiltration both in- and outside the irradiated field • Serum immune phenotype at baseline and after avelumab + S B RT • Concordance of imaging using diffusion- weighted and DCE - MRI, and PET with biopsy sample results Patient Population Patients with a histologically/cytologically proven malignant pleural or peritoneal mesothelioma who have received one or more lines of standard treatment. Number of Patients 27 patients maximum 13 patients will be recruited for Stage 1.