Table 1.

Inclusion and exclusion criteria for participating patients

Inclusion criteria

- Age of 18 years or older - Pathologically confirmed advanced stage cutaneous melanoma (stage III or IV) requiring systemic treatment with anti-PD-1: ○ In case of stage IV disease, only patients with M1a or M1b disease are eligible - Confirmed disease progression (≥ 20% increase or measurable recurrence according to RECIST 1.1) on two consecutive scans with a four-week interval while on anti-PD-1 treatment, of which the second scan has to be performed within three weeks prior to signing informed consent - Measurable disease per RECIST 1.1 criteria - ECOG performance status of 0–1 - Life expectancy of > three months - Adequate organ function as determined by standard-of-care lab (including serum ALT/AST < 3 × the upper limit of normal (ULN); serum creatinine clearance ≥ 50 mL/min; total bilirubin ≤ 20 μmol/L, except in patients with Gilbert’s Syndrome who must have a total bilirubin < 50 μmol/L) - LDH level of ≤ 1 × ULN - Use of highly effective method of birth control during treatment (for both genders) - Able to understand and sign the informed consent form

Exclusion criteria

- Acral, uveal or mucosal melanoma or an unknown primary - Previous treatment for melanoma other than anti-PD-1 treatment - Stage IV with M1c or M1d disease - Autoimmune diseases (e.g. history of inflammatory bowel disease, including ulcerative colitis and Crohn’s disease (this does not include Hashimoto thyroiditis, vitiligo, or history of psoriasis without active disease)) - Any grade 3 or 4 irAE still requiring active immunosuppressive medication, apart from endocrinopathies that are stable under hormone replacement therapy. Patients who have developed grade 3–4 irAEs, which have reverted to grade 1 with immunosuppressive drugs and who are off immunosuppression at least two weeks prior to enrollment are eligible - Brain or LM metastasis - Elevated LDH level - History of major gastric, esophageal or bowel surgery (e.g. Wipple procedure, subtotal colectomy) - Severe food allergy (e.g. nuts, shellfish) - Swallowing disorders or expected bowel passage problems (e.g. ileus, fistulas, perforation) - Severe dysphagia with incapability of swallowing one liter of bowel lavage - Life expectancy of < three months - Severe cardiac or pulmonary comorbidities (per judgement of the investigator) - Women who are pregnant or breastfeeding - Active systemic infections, coagulation disorders or other active major medical illnesses - Other malignancies, except adequately treated and with a cancer-related life expectancy of > five years - Treatment with antibiotics in the three months prior to study enrollment, or expectation to receive antibiotics during the course of this study