• I1. Male or female ≥ 18 years at the day of consenting to the study;

• I2. Patients must have histologically confirmed diagnosis of GIST (within the French Reference Network in Pathology of Sarcomas - RRePS network); archival tumor sample must be made available for translational research program (in case there is no sufficient archival tumor material available, a biopsy must be performed prior to treatment start); Nota Bene: mutational status and level of expression of PD1/PD-L1 will not be considered as selection criteria but will be studied as endpoints for translational objectives.

• I3. Locally advanced or metastatic disease confirmed as measurable according to the RECIST V1.1 (Appendix 1);

• I4. Patients who previously failed to at least imatinib, sunitinib and then regorafenib. Failure is defined for Imatinib as progressive disease, and for sunitinib and regorafenib as progressive disease and/or intolerance;

• I5. Performance Status of the ECOG of 0 or 1;

• I6. Adequate bone marrow and organ function defined by the following laboratory results:

• a. Bone marrow: i. Hemoglobin ≥ 9.0 g/dl, ii. Absolute Neutrophils Count (ANC) ≥ 1.5 G/l, iii. Lymphocytes count ≥ 0.5 G/l, iv. Platelets ≥ 100 G/l;

• b. Coagulation: i. Prothrombin time ≤ 1.5 x Upper Limit of the Normal (ULN) for patients without therapeutic anticoagulation.

• Patients with therapeutic anticoagulation must have stable dose of treatment.

• c. Hepatic function: i. Total serum bilirubin ≤ 1.5 x ULN (except patients with Gilbert's syndrome who must have total serum bilirubin ≤ 3.0 x ULN), ii. Transaminases (ASAT/ALAT) ≤ 2.5 x ULN (or ≤ 5.0 x ULN in case of documented liver metastases) iii. Alkaline Phosphatases ≤ 2.5 x ULN (or ≤ 5.0 x ULN in case of documented bone metastases),

• d. Renal function: i. Serum creatinine ≤ 1.5 x ULN or Cr. Cl. ≥ 40ml/min/1.73m² (MDRD or CKD-EPI formula);

• I7. Willingness and ability to comply with the study requirements;

• I8. Signed and dated informed consent indicating that the patient has been informed of all the aspects of the trial prior to enrolment;

• I9. Women of childbearing potential are required to have a negative serum pregnancy test within 72 hours prior to study treatment start. A positive urine test must be confirmed by a serum pregnancy test;

• I10. Women of childbearing potential and male patients must agree to use adequate highly effective contraception for the duration of study participation (Appendix 3);

• I11. Patient must be covered by a medical insurance;