Assessing the Tolerance and Clinical Benefit of feCAl tranSplantation in patientS With melanOma

Inclusion Criteria:

• Patients aged 18 to 80

• Patients with unresectable or metastatic melanoma

• Patients with ECOG performance of 0-2

• Patients able to provide written informed consent and understand the risksassociated with MaaT013

• Have measurable disease as per RECIST version 1.1, on a tumor evaluation (either CTscan, physical evaluation or ultrasonography) performed less than 2 weeks beforescreening visit

• Requiring a treatment with Ipilimumab and PD1 inhibitor (Nivolumab) and having nocontraindication to these drugs nor to their excipients

• Patients unexposed to ipilimumab and anti PD1 or anti PDL1 except if they havereceived it in the adjuvant setting (if the last dose of Ipilimumab® or anti PD1 oranti PDL1 was received at least 6 months before randomization).

• Negative pregnancy test (serum)

• Women of childbearing potential (WOCBP) must agree to follow instructions formethod(s) of contraception for the duration of study treatment with nivolumab,ipilimumab and 6 months after the last dose of study treatment (ie, 30 days (duration of ovulatory cycle) plus the time required for the investigational drug toundergo approximately five half-lives)

• Males who are sexually active with WOCBP must agree to follow instructions formethod(s) of contraception for the duration of study treatment with nivolumab,ipilimumab and 7 months after the last dose of study treatment {i.e., 90 days (duration of sperm turnover) plus the time required for the investigational drug toundergo approximately five half-lives.}

• Hemoglobin ≥9 g/dL

• Platelets ≥ 100000mm3

• Neutrophils ≥ 1500/mm3

• Creatinine Clearance ≥ 50mL/mn

• AST ≤ 3N

• ALT ≤ 3N

• Total bilirubin ≤ 1.5N (except subjects with Gilbert Syndrome, who can have totalbilirubin < 3.0 mg/dL)

• Alkaline phosphatase ≤ 3N

• INR < 1.5

• Prothrombin ≥ 70%

• TCA < 1.2

• No Hepatocellular insufficiency

Exclusion Criteria:

• Pregnant or breastfeeding women

• Antibiotics in the last two weeks prior to the FMT

• Inability to retain enemas

• Expected to require any other form of systemic or localized anti-neoplastic therapywhile on study

• Active infection requiring systemic therapy.

• Active, known or suspected autoimmune disease.

• No health insurance,

• Patients already included in a clinical research other than an observational study (e.g: registry, cohort).

• Patient on AME (state medical aid) (unless exemption from affiliation)

• Patients guardianship/legal protection/curatorship

• Contraindication to fecal transplantation

• Known hypersensitivity to Normacol or Moviprep® or equivalent patent medicines enemaor one of their components.

• Fluid-electrolyte disorders with sodium retention (heart failure,hyperaldosteronism, drug-induced edema)

• Recent acute coronary syndrome or unstable ischemic heart disease

• Congestive heart failure ≥ Class III or IV as defined by New York Heart Association

• Hypersensitivity to the active substances or to any of the excipients: Aspartame (E951), Acesulfame, potassium (E950), lemon flavor (maltodextrin, citral, lemonessential oil, lime essential oil, xanthan gum, vitamin E)

• Gastrointestinal obstruction or perforation

• Gastric emptying disorders (gastroparesis),

• Ileus,

• Phenylketonuria (due to the presence of aspartame),

• Deficiency in glucose-6-phosphate dehydrogenase (due to the presence of ascorbate),

• Toxic megacolon, in severe forms of inflammation of the intestinal tract, includingCrohn's disease and ulcerative colitis.