Preventing adverse events in patients with renal cell carcinoma treated with doublet immunotherapy using fecal microbiota transplantation (FMT): Initial results from perform a phase I study.

4553 Background: The treatment landscape of metastatic renal cell carcinoma (mRCC) has evolved with the advent of either dual immune checkpoint inhibition (ICI) or in combination with Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor. Gut microbiota plays a central role in developing local and systemic immunity, with potential influence in controlling anti-tumor immune response in cancer patients treated with ICI. We hypothesize that FMT from healthy donors given before immunotherapy will establish a more resilient gut microbiota, reducing the treatment toxicity and improving response to therapy. PERFORM is an ongoing phase I study evaluating the safety of FMT and immunotherapy combination in first-line (1L) mRCC, and assessing whether FMT will prevent or mitigate immune-related adverse events (irAE). Methods: Eligible patients with untreated mRCC received a full dose and 2 supportive FMT procedures prior to the first 3 cycles of doublet ICI or in combination with VEGF-TKI. Primary endpoint is the feasibility and safety of combining FMT using intestinal bacteria existing in the stool of healthy donors with immunotherapy. Secondary endpoints include incidence of irAEs, objective response rate (ORR; RECIST v1.1), and changes in pts microbiome and immune profile post-FMT. We included a preliminary analysis of the first 10 patients. Results: 10 patients received FMT and doublet ICI therapy (10 ongoing). 8/10 (80%) patients were male. Median Age: 59.5 (53-71) years-old. Most common histology was clear cell RCC (90%) and all patients had an intermediate or poor-risk disease. 93.3% of planned FMT were administered. No dose-limiting toxicities due to FMT were observed. Median (range) follow-up was 5.5 (1–22) months. 4 patients (40%) discontinued treatment due to irAEs: colitis (n = 3), arthritis (n = 1). IrAEs were reported in 8 (80%) patients, including diarrhea (n = 6; 60%) and skin rash (n = 2, 20%). Grade 3/4 AEs were experienced by 6 (60%) patients, including colitis (n = 4, 40%). ORR was confirmed in 4/9 patients (44%; 95% CI, 30–60); 1 (11%) partial response. Microbiota and immune analysis data to be presented. Conclusions: The role of microbiome modification in preventing immune-related toxicities by adding FMT to ICI therapy was associated with a safety profile in unselected 1L mRCC and promising clinical efficacy data. Further prospective studies to examine the changes in the immune and microbiota profiles to determine biomarkers related to healthy outcomes/less frequent toxicities in patients receiving immunotherapy are warranted. Clinical trial information: NCT04163289.