Study population and eligibility criteria
vitiligo, Wegener’s granulomatosis, cardiac criteria:- Congestive heart failure, Unstable angina, ’s syndrome, renal cell carcinoma, autoimmune disease, eczema, angina symptoms, thrombosis, new-onset angina, vasculitis, head and neck carcinoma, psoriasis, psoriatic arthritis, bladder cancer, autoimmune-related hypothyroidism, thyroid replacement hormone, ): renal cell carcinoma, ):
RHEUMATOID ARTHRITIS, VITILIGO, RECURRENCE, INFLAMMATORY BOWEL DISEASE, GLOMERULONEPHRITIS, TYPE I DIABETES MELLITUS, UNSTABLE ANGINA, MULTIPLE SCLEROSIS, RENAL CELL CARCINOMA, HEART, LIVER METASTASIS, AUTOIMMUNE DISEASE, ECZEMA, LICHEN SIMPLEX CHRONICUS, THROMBOSIS, SYSTEMIC LUPUS ERYTHEMATOSUS (SLE), VASCULITIS, ANTIPHOSPHOLIPID SYNDROME, PSORIASIS, PSORIATIC ARTHRITIS, BLADDER CANCER, NON-SMALL CELL LUNG CANCER, METASTATIC CANCER, SYSTEMIC IMMUNE ACTIVATION, DISEASE PROGRESSION, RENAL CANCER, DISEASE, MYOCARDIAL INFARCTION
Patients will be included in different cohorts, depending on the type of histologically proven metastatic cancer:
Cohort 1 (phase I and expansion cohorts phase) : non-small cell lung cancer without oncogenic addiction (EGFR/ALK/ROS/BRAF) that progresses after platinum-based chemotherapy and immunotherapy given as sequential or concomitant therapyCohort 2 (expansion cohorts phase only) : bladder cancer that progresses after platinum-based therapy with or without maintenance with anti-PD-1/PD-L1Cohort 3 (expansion cohorts phase only): renal cell carcinoma in second-line therapy that progresses after a first-line administered according to the guidelines for the standard of care in renal cancer. First-line therapy could include an antiangiogenic agent, a tyrosine kinase inhibitor, alone or associated with immunotherapy (anti-PD-L1, anti-CTLA4)Cohort 4 (expansion cohorts phase only): head and neck carcinoma at the first line of locoregional or metastatic recurrence. The patient should not be eligible for surgery.Study inclusion and exclusion criteria are detailed in Tables 
Study inclusion criteria.7. Participant must have following advanced disease and must not be a candidate for other approved therapeutic regimen known to provide significant clinical benefit based on investigator judgement :- Cohort 1 (phase I and expansion cohorts phase) : non-small cell lung cancer without oncogenic addiction (EGFR/ALK/ROS/BRAF) which progress after platin based chemotherapy and immunotherapy given as sequential or concomitant therapy - Cohort 2 (expansion cohorts phase only) : bladder cancer which progress after platin based therapy with or without maintenance with anti PD-1/PD-L1- Cohort 3 (expansion cohorts phase only) : renal cell carcinoma in second-line therapy which progress after a first line administered according to the guidelines for the standard of care in renal cancer. First line therapy could include antiangiogenic agent, tyrosine kinase inhibitor, alone or associated with immunotherapy (anti-PD-L1, anti-CTLA4) - Cohort 4 (expansion cohorts phase only) : head and neck carcinoma at the first line locoregional or metastatic recurrence. Patient should not be eligible to surgery.8. Participants who received prior anti-PD-1/L1 therapy must fulfill the following requirements- Have achieved a complete response, partial response or stable disease and subsequently had disease progression while still on anti-PD-1/L1 therapy- Have received at least two doses of an approved anti-PD-1/L1 therapy (by any regulatory authority)- Have demonstrated disease progression as defined by RECIST v1.19. Adequate hematological, renal, metabolic and hepatic functions:- Hemoglobin ≥ 9 g/dl (participants may have received prior red blood cell [RBC] transfusion, if clinically indicated (but should be performed with 1 week delay between transfusion and validation of eligibility criteria); absolute neutrophil count (ANC) ≥ 1.5 G/l, platelet count ≥ 100 G/l, white blood cell count ≥ 2.5 G/l (or within local laboratory normal limits) and lymphocyte count ≥ 0.75 G/l-. Alkaline phosphatase (AP), alanine aminotransferase (ALT) and aspartate aminotransferase (ASP) ≤ 2.5 x upper limit of normality (ULN) (≤ 5 x ULN in case of extensive skeletal involvement for AP exclusively and ≤ 5 x ULN in case of liver metastasis for AST and ALT).- Total bilirubin ≤ 1.5 x ULN, (3 x ULN for gilbert disease)- Albumin ≥ 25 g/l.- Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance (CrCl) ≥ 30 ml/min (according to Cockcroft and Gault formula).- INR ≤ 1.5 x ULN- aPTT ≤ 1.5 X ULN- Serum calcium within normal laboratory ranges,
Study exclusion criteria.10. 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%15. 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 dermatologicmanifestations < 10% of the skin (e.g., participants with psoriatic arthritis would be excluded) are eligible