Phase II Multicentric Study of Pembrolizumab in Classic or Endemic Kaposi's Sarcoma

Inclusion Criteria:

* Classic or endemic histologically confirmed KS
* Progressive disease
* KS with more than 10 lesions or involving more than one limb segment or with involvement \>3% body surface
* KS with at least 4 lesions ≥5mm
* KS with at least 1 other cutaneous tumor available for repeated pharmacodynamics evaluation and be willing to provide tissue from cutaneous biopsy of a tumor lesion
* At least 4 weeks washout for all KS specific therapies including chemotherapy and immunotherapy
* Provide written, informed consent prior to the performance of any study specific procedures
* Be ≥ 18 years of age on day of signing informed consent.
* Have a performance status of 0 or 1 on the ECOG Performance Scale.
* Demonstrate adequate organ function:

Hematological : Absolute neutrophil count (ANC) ≥1,000/mm3, Platelets ≥100,000 / mm3, Hemoglobin ≥ 9 g/dL Renal: Calculated creatinine clearance ≥40 mL/min (using Modification of diet in renal disease (MDRD) formula) Hepatic: AST (SGOT) and ALT (SGPT) ≤ 2.5xULN, serum total bilirubin ≤ 1.5xULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels \>1.5xULN.

* Female subject of childbearing potential should have a negative serum pregnancy within 72 hours prior to receiving the first dose of study medication
* Have a health insurance

Exclusion Criteria:

* Has a known history of organ transplantation or HIV (HIV 1/2 antibodies detected at selection) Is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
* Has KS with symptomatic visceral involvement unless no other therapeutic option is available Previously received treatments with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4 antibody or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
* Has a known history of active infectious hepatitis, type B (HBsAg detected) or C (HCV RNA detected) or active TB (Tuberculosis Bacillus).
* Has an active infection requiring systemic therapy.
* Has hypersensitivity to pembrolizumab or any of its excipients.
* Has had a prior anti-cancer monoclonal antibody (mAb) within last 4 weeks or who has not recovered (i.e., \> Grade 1 at selection) from adverse events due to agents administered more than 4 weeks earlier.
* Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 3 weeks prior to study Day 1 or who has not recovered (i.e., \> Grade 1 at selection) from adverse events due to a previously administered agent (Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study). (Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy).
* Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
* Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with vitiligo, type I diabetes mellitus, hypothyroidism, psoriasis non requiring systemic treatment are permitted to enroll.
* Has active non-infectious pneumonitis or known history of non-infectious pneumonitis that required steroids, severe pulmonary disease or hypoxia
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
* Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, or not willing to use adequate contraceptive methods from study Visit 1 throughout the study period up to 120 days after the last dose of study therapy.
* Has received a live vaccine within 30 days prior to the first dose of trial treatment or while participating in the trial.
* Is currently participating or has participated in a study of an investigational agent within 4 weeks of the first dose of treatment.
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
* Patient under guardianship or curators