FMT to Convert Response to Immunotherapy

Inclusion Criteria:

• Patients should be 18 years or older

• Patients have pathologically confirmed advanced stage cutaneous melanoma (stage IIIor IV) requiring systemic treatment with anti-PD-1

• In case of stage IV disease, only patients with M1a or M1b disease areeligible.

• Patients have confirmed disease progression (≥20% increase according to RECIST1.1)on two consecutive scans with a four week interval while on anti-PD-1 treatment, ofwhich the second scan has to be performed within 3 weeks prior to signing informedconsent.

• Patients must have measurable disease per RECIST 1.1 criteria

• Patients have an ECOG performance status of 0-1 (appendix D)

• Patients have a life expectancy of >3 months

• Patients have adequate organ function as determined by standard-of-carepre-checkpoint inhibitor infusion lab (including serum ALAT/ASAT less than threetimes the upper limit of normal (ULN); serum creatinine clearance 50ml/min orhigher; total bilirubin less than or equal to 20 micromol/L, except in patients withGilbert's Syndrome who must have a total bilirubin less than 50 micromol/L)

• Patients have an LDH level of ≤1 times ULN

• Patients of both genders must be willing to use a highly effective method of birthcontrol during treatment

• Patients must be able to understand and sign the Informed Consent document

Exclusion Criteria:

• Patients with acral, uveal or mucosal melanoma, or patients with an unknown primary

• Patients who have received treatment for their melanoma other than anti-PD-1treatment.

• Stage IV patients with M1c or M1d disease.

• Patients with autoimmune diseases: patients with a history of inflammatory boweldisease, including ulcerative colitis and Crohn's disease, are excluded from thisstudy (except Hashimoto thyroiditis, vitiligo, history of psoriasis, but no activedisease)

• Patients with any grade 3 or 4 immune-related adverse events still requiring activeimmunosuppressive medication, apart from endocrinopathies that are stable underhormone replacement therapy. Patients who had developed grade 3-4 immune relatedtoxicity, which has reverted to grade I with immunosuppressive drugs and who are offimmunosuppression at least two weeks prior to enrollment are eligible

• Patients with brain or LM metastasis.

• Patients with an elevated LDH level

• Patients that have undergone major gastric/esophageal/bowel surgery (like Wipple,subtotal colectomy)

• Severe food allergy (e.g. nuts, shellfish)

• Patients with a swallowing disorder or expected bowel passage problems (ileus,fistulas, perforation)

• Severe dysphagia with incapability of swallowing 2 liters of bowel lavage

• Patients with a life expectancy of less than three months

• Patients with severe cardiac or pulmonary comorbidities (per judgement of theinvestigator)

• Women who are pregnant or breastfeeding

• Patients with any active systemic infections, coagulation disorders or other activemajor medical illnesses

• Patients with other malignancies, except adequately treated and a cancer-relatedlife-expectancy of more than 5 years

• Patients who received treatment with antibiotics in the three months prior to studyenrolment, or patients we are expected to receive systemic antibiotics during thecourse of this study