Fecal Microbiota Transplant (FMT) in Melanoma Patients

This is a phase II Simon two-stage single-center study of concurrent fecal microbiota transplang (FMT) with pembrolizumab in patients with PD-1 resistant/refractory melanoma. The study will be conducted over a 12-week period (and up to 24-weeks in responding patients).

Patient eligibility is based upon prior exposure to PD-1 inhibitor therapy and response at first (or subsequent) restaging scans from week 12 up to week 52. Patients must have received a minimum of 2 cycles to be considered eligible. Patients who have received either nivolumab or pembrolizumab are eligible. Patients who have received pembrolizumab/nivolumab in combination with other investigational agent(s) may be eligible at the discretion of the treating investigator. PD-1 refractory disease is defined as progressive disease (PD) at the first (or subsequent) radiographic evaluation while receiving PD-1 inhibitor treatment as assessed by RECIST v1.1 on a restaging scan. Other eligibility criteria include absence of CNS disease, presence of disease amenable to biopsy and lack of contra-indications to FMT administration. Patients will be stratified on the presence or absence of liver metastases.

Suitable patients will be identified following first (or subsequent) restaging study that documents progressive disease (RECIST v1.1). Patients will undergo a screening evaluation consisting of imaging (including CNS if clinically suspected), tumor biopsy, and serological/stool studies to confirm suitability for FMT administration. Eligible patients will receive FMT endoscopically (along with intestinal biopsy) (with cycle 1 pembrolizumab +/- 3 days) followed by 3 further cycles of pembrolizumab (cycles 2-4) following which restaging will be performed. Patients with stable and/or responding disease will continue to receive pembrolizumab on study for 4 cycles. Patients with stable and/or responding disease after 8 cycles of pembrolizumab will continue to receive therapy off study until disease progression or up to two years from FMT administration.