Spartalizumab and Low-dose PAzopanib in Refractory or Relapsed Solid TumOrs of Pediatric and Adults

Inclusion Criteria: 1. For pediatric patients (Cohort 1): 1. Patients should be without standard established therapeutic alternatives at the time of enrollment suffering from the following conditions : * refractory or recurrent solid tumor, proven histologically, * any tumor with high mutational load (\> 10 somatic mutations/ Mo) or a high MSI status, * tumor, whatever the histology, with proven PDL1 expression (≥1%) or presence of mature tertiary lymphoid structure (TLS). 2. Age ≥5 and \<18 years at inclusion, patients 18 years and older may be included after discussion with the Sponsor if they have a pediatric recurrent/refacractory malignancy. 3. Performance status: Karnofsky performance status (for patients \>16 years of age) or Lansky Play score (for patients ≤16 years of age) ≥70%. Patients who are unable to walk because of paralysis or stable neurological disability, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. 4. Able to swallow tablets. 5. Evaluable or measurable disease as defined by standard imaging criteria for the patient's tumor type (RECIST v1.1…). 6. Life expectancy ≥ 3 months. 7. Adequate organ function: * Hematologic criteria :peripheral absolute neutrophil count (ANC) ≥1000/μL (unsupported), platelet count ≥100,000/μL (unsupported), hemoglobin ≥8.0 g/dL (transfusion is allowed) * Cardiac function: shortening fraction (SF) \>29% (\>35% for children \<3 years) and left ventricular ejection fraction (LVEF) ≥50% at baseline, as determined by echocardiography (mandatory only for patients who have received cardiotoxic therapy), absence of QTc prolongation (QTc \>450 msec on baseline ECG, using the Fridericia correction \[QTcF formula\]) or other clinically significant ventricular or atrial arrhythmia. * Renal and hepatic function: serum creatinine ≤1.5 x upper limit of normal (ULN) for age, total bilirubin ≤1.5 x ULN, alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 x ULN; aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase/SGOT ≤ 2.5 x ULN except in patients with documented tumor involvement of the liver who must have AST/SGOT and ALT/SGPT ≤ 5 x ULN. 8. Able to comply with scheduled follow-up and with management of toxicity. 9. Females of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 72 hours prior to initiation of treatment. Sexually active women of childbearing potential must agree to use a highly effective contraception during the study and for at least 6 months after the last study treatment administration. Sexually active male patients must agree to use condoms during the study and for at least 6 months after the last study treatment administration. 10. Written informed consent from parents/legal representative and age-appropriate assent before any study-specific screening procedures are conducted according to local, regional or national guidelines. 11. Patient affiliated to a social security regimen or beneficiary of the same according to local requirements. 2. For adults patients: * Pre-screening phase: 1. adults (≥ 18 years old) with refractory or recurrent solid tumor (include rhabdomyosarcoma, Ewing's sarcoma, osteosarcoma and other) and/or tumor with High mutation rate (\>10 somatic mutations/Mb) and/or suffering of Mismatch repair-deficient syndrome. 2. Adult patients with an ECOG score of 0/1. Patients who are unable to walk because of paralysis or stable neurological disability, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. 3. Evaluable or measurable disease as defined by standard imaging criteria for the patient's tumor type (RECIST v1.1…). 4. Written informed consent from patient before any study-specific screening procedures are conducted according to local, regional or national guidelines. * Screening phase (Cohort 2): 1. adults without standard established therapeutic alternatives at the time of enrollment suffering from refractory or recurrent advanced solid tumor characterized by the presence of mature TLS 2. Age ≥ 18 years at inclusion 3. Adult patients with an ECOG score of 0/1. Patients who are unable to walk because of paralysis or stable neurological disability, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. 4. Evaluable or measurable disease as defined by standard imaging criteria for the patient's tumor type (RECIST v1.1…). 5. Life expectancy ≥ 3 months 6. Adequate organ function: * Hematologic criteria :peripheral absolute neutrophil count (ANC) ≥1000/μL (unsupported), platelet count ≥100,000/μL (unsupported), hemoglobin ≥8.0 g/dL (transfusion is allowed) * Cardiac function: shortening fraction (SF) \>29% and left ventricular ejection fraction (LVEF) ≥50% at baseline, as determined by echocardiography (mandatory only for patients who have received cardiotoxic therapy), absence of QTc prolongation (QTc \>450 msec on baseline ECG, using the Fridericia correction \[QTcF formula\]) or other clinically significant ventricular or atrial arrhythmia. * Renal and hepatic function: serum creatinine ≤1.5 x upper limit of normal (ULN) for age, total bilirubin ≤1.5 x ULN, alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 x ULN; aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase/SGOT ≤ 2.5 x ULN except in patients with documented tumor involvement of the liver who must have AST/SGOT and ALT/SGPT ≤5 x ULN. g. Able to comply with scheduled follow-up and with management of toxicity. h. Females of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 72 hours prior to initiation of treatment. Sexually active women of childbearing potential must agree to use a highly effective contraception during the study and for at least 6 months after the last study treatment administration. Sexually active male patients must agree to use condoms during the study and for at least 6 months after the last study treatment administration. i. Written informed consent from patient before any study-specific screening procedures are conducted according to local, regional or national guidelines. j. Patient affiliated to a social security regimen or beneficiary of the same according to local requirements. Exclusion Criteria: For pediatric and adult patients (Cohorts 1 and 2): 1. Patients treated with anti-PD1 immunotherapy within 6 months prior to starting study treatment; patients treated with anti-PD1 for more than 6 months remain eligible for inclusion, provided that this treatment has brought the patient clinical benefit (objective response or stable disease \> 4 months). 2. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea or malabsorption syndrome). 3. Clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmia, e.g. ventricular, supraventricular, nodal arrhythmias, or conduction abnormality), unstable ischemia, congestive heart failure within 12 months of screening). 4. Uncontrolled hypertension 5. Active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection. 6. Presence of any ≥ CTCAE grade 2 treatment-related toxicity with the exception of alopecia, ototoxicity or peripheral neuropathy. 7. Systemic anticancer therapy within 21 days of the first study dose or 5 times its half-life, whichever is less. 8. Previous myeloablative therapy with autologous hematopoietic stem cell rescue within 8 weeks of the first study drug dose 9. Allogeneic stem cell transplant within 3 months prior to the first study drug dose. Patients receiving any agent to treat or prevent graft-versus host disease (GVHD) post bone marrow transplant are not eligible for this trial. 10. Radiotherapy (non-palliative) within 21 days prior to the first dose of drug (or within 6 weeks for therapeutic doses of MIBG) 11. Major surgery within 21 days of the first dose. Gastrostomy, ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumor biopsy and insertion of central venous access devices are not considered major surgery, but for these procedures, a 48-hour interval must be maintained before the first dose of the investigational drug is administered. 12. Currently taking medications with a known risk of prolonging the QT interval or inducing Torsades de Pointes 13. High dose chemotherapy followed by peripheral stem cell transplantation within less than 6 months. 14. Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids (up to 0.25 mg/kg daily prednisone equivalent) may be approved after consultation with the Sponsor. 15. Diagnosis of prior or active autoimmune disease. 16. Evidence of interstitial lung disease. 17. Unable to taper steroids due to ongoing mass effect; a maximum dexamethasone dose of 0.05 mg/kg/day is allowed, but preferably have been discontinued. 18. Known hypersensitivity to any study drug or component of the formulation. 19. Persons referred to in Articles L. 1121-5, L. 1121-6, L. 1121-8 and L. 11221-1-2 of the Public Health Code (pregnant women, parturient and nursing mothers; persons deprived of their liberty by a judicial or administrative decision, persons hospitalized without consent and persons admitted to a health or social establishment for purposes other than that of research; adults subject to a legal protection measure or incapacitated express consent; people in emergency situations who cannot give prior consent) 20. Vaccinated with live, attenuated vaccines within 4 weeks of the first dose of study drug.