IMMUNOs-SBRT

• Evidence of symptomatic central nervous system (CNS) or leptomeningeal metastases,
• Women who are pregnant or breast feeding,
• Participation in a study involving a medical or therapeutic intervention in the last 30 days,
• Previous enrolment in the present study,
• Participant unable to follow and comply with the study procedures because of any geographical, familial, social or psychological reasons,
• Known hypersensitivity to any involved study drug or of its formulation components,
• History of severe allergic anaphylactic reactions to chimeric, human or humanized antibodies, or fusion proteins,
• Treatment with systemic immunosuppressive medications including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents within 2 weeks prior to inclusion. Systemic corticosteroids is not allowed but at physiologic doses meaning less than 10 mg/day of prednisone or its equivalent. The use of inhaled corticosteroids and mineral corticoids is allowed.
• Major surgical procedure, open biopsy or significant traumatic injury within 28 days before inclusion,
• Any of the following cardiac criteria:

Congestive heart failure ≥ New York Heart Association (NYHA) class 2,

• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months), Myocardial infarction less than 6 months before inclusion Uncontrolled cardiac arrhythmias, Known left ventricular ejection fraction (LVEF) <50%
• Individuals deprived of liberty or placed under legal guardianship, curatorship or judicial protection.
• Prior organ transplantation, including allogeneic stem cell transplantation,
• Known clinically significant liver disease, including, alcoholic, or other hepatitis, cirrhosis, fatty liver and inherited liver disease, active viral with positive viralDNA detection.
• History of intra-abdominal inflammatory process within the last 12 months such as, but not limited to, diverticulitis, peptic ulcer disease or colitis.
• History of autoimmune disease including, but not limited to systemic lupus erythematosus (SLE), Sjögren's syndrome, glomerulonephritis, multiple sclerosis, rheumatoid arthritis, vasculitis, systemic immune activation, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Guillain-Barré syndrome, Bell's palsy.

Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible, Participants with controlled Type I diabetes mellitus on a stable insulin regimen are eligible, Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with only dermatologic manifestations <10% of the skin (e.g., participants with psoriatic arthritis would be excluded) are eligible.

• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Poorly controlled Type II diabetes mellitus defined as a screening fasting plasma glucose ≥160 mg/dL (or 8.8 mmol/L).
• Severe infections within 2 weeks prior to inclusion, including but not limited to SARS-Cov-2 infection, hospitalization for complications of infection, bacteremia, or severe pneumonia.
• Received therapeutic oral or IV antibiotics within 2 weeks prior to inclusion. Participants receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
• Any contraindication to tumor biopsy,
• Participant with spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >2 weeks prior to inclusion.
• Administration of a live, attenuated vaccine within 4 weeks before the start of study medication or anticipation that such a live attenuated vaccine will be required during the study. Influenza vaccination is allowed during influenza season only (approximatively October to March).
• Patient with a known history of Human Immunodeficiency Virus (HIV) (HIV1/2 antibodies) or known acquired immunodeficiency syndrome (AIDS),
• Patients with EBV infection (Positive EBV viral capsid antigen IgM test at screening)
• Active tuberculosis
• Concomitant use of prohibited concomitant therapy (cf paragraph 6.5.2.2) or anticipation that such concomitant medication/therapies will be required during the study
• For NSCLC indication, patients with lymphoepithelioma-like carcinoma are excluded.