Stool donor qualification and collection from metastatic melanoma (MM) patients (pts) who have responded to checkpoint inhibitors (CPI) for manufacturing of fecal microbiota transplantation (FMT).

Abstract

TPS146 Background: There have been remarkable improvements in responses rates (RR) and outcomes for pts with MM with the use of single agent CPIs. However, only 35% of pts respond to therapy and less than 10% achieve a complete response (CR). Although CPIs are approved for advanced MM treatment, there is a critical need to identify predictors of response and improve outcomes for these pts, the majority of whom will die from their disease. In an analysis of stool from MM pts prior to receiving CPI (anti-PD1), MD Anderson reported the association of higher alpha diversity and a favorable “Type I” signature with improved RR and prolonged PFS. Subsequently, FMT in mice via oral gavage using stool from CR MM pts responding to anti-PD1 with a favorable microbiome signature and treated with CPI demonstrated improved RR compared to FMT with stool from non-responders. Although FMT has been studied and has shown efficacy in other diseases, clinical safety and utility in pts with MM requires investigation. We hypothesize that FMT from MM pts with CR to CPIs and a Type I signature will be tolerable and demonstrate favorable outcomes. Methods: To initiate the testing of this hypothesis, we designed a study to identify and screen pts with MM who have responded to anti-PD1 for FMT stool donation. Pts must be in CR from MM for 6 months on 2 consecutive scans. Screening procedures per standard practice of approved INDs for FMT include health history questionnaires, physical exam, confirmation of current disease status, infectious disease screening, and an evaluation of the stool sample to ensure Type I signature requirements. Notably, there have been specific modifications made to this protocol in donor eligibility criteria, as accepted by the FDA, to accommodate this unique patient population. Participants will donate stool for up to 4 weeks and may be considered for subsequent donation cycles after undergoing re-screening. Stool will be manufactured into capsule form and used in the clinical trial. This study is open and active at three sites, MD Anderson, MGH, and DFCI.