The DIET study: A randomized controlled trial of a high fiber diet in cancer patients (pts) receiving immune checkpoint blockade (ICB).
Authors: Farias Rachel , Jiang Yan , Jenkins Courtney A , Levy Erma J , Montalvo Marco , Duncan Sheila , Sirmans Elizabeth , Rains Justin , Wang Jian , Kuss Tessa M , Burton Elizabeth M. , Ajami Nadim J. , Wargo Jennifer Ann , Daniel-MacDougall Carrie , McQuade Jennifer Leigh 
Published: June 2023

TPS9609 Background: Gut microbiome modulation is a promising strategy to enhance response to ICB Fecal microbiota transplant studies have shown positive signals of improved outcomes in both ICB naïve and refractory melanoma; however, this strategy is challenging to scale. Diet is a key determinant of the gut microbiota and we have previously shown that a) habitual high dietary fiber intake is associated with improved response to ICB and b) fiber manipulation in mice impacts ant-tumor immunity. We recently demonstrated feasibility of a controlled high-fiber dietary intervention (HFDI) conducted in melanoma survivors with excellent compliance and tolerance. Building on this, we are now conducting a single center Phase II randomized trial of HFDI versus healthy control diet in cancer pts receiving ICB (NCT04645680). Methods: 57 pts starting standard of care (SOC) ICB will be enrolled in 4 cohorts: 3 melanoma cohorts in the adjuvant (n = 21), neoadjuvant (n = 12), and unresectable (n = 12) settings and 1 metastatic renal cell carcinoma (RCC) cohort (n = 12). Key inclusion criteria include BMI 18.5-40 kg/m2, and willingness to exclusively eat the diet. Key exclusion criteria include diabetes mellitus, inflammatory bowel disease, total colectomy or bariatric surgery, recent use of prebiotic/probiotic supplements, steroids (within 14 days), antibiotics (within 21 days), current smoker or heavy drinker, and dietary fiber > 20g/day. Pts are randomized 2:1 to the HFDI (target fiber 50g/day) or control diet (fiber 15-20g/day) stratified by BMI and cohort. Both diets have same macronutrient composition but differ in fiber content. The primary objective is to establish the effects of a dietary intervention on the structure and function of the gut microbiome. Secondary endpoints include change in circulating and stool metabolites, systemic and tumor immunity, and safety and tolerability of dietary intervention. As a controlled feeding study, all meals are isocaloric and prepared by MD Anderson Bionutrition Research Core for up to 11 weeks. Meals follow American Cancer Society and American Institute for Cancer Research recommendations which include whole foods plant-forward diet, little to no processed meats or added sugars, and no alcohol consumption. Meals are shipped weekly within the contiguous United States and include breakfast, lunch, dinner, and snacks. The HFDI group start at 30g fiber/day, up titrated every 2 weeks up to 50g/day based on tolerance. Blood and stool samples are collected longitudinally. Tumor biopsies are required in the neoadjuvant cohort and optional in unresectable. A Fitbit is provided to monitor physical activity and a scale to measure daily weight. 24 of the planned 57 pts have been enrolled: n = 13 adjuvant, n = 5 neoadjuvant, n = 5 unresectable, n = 1 RCC. 14 treated with PD1 monotherapy, 9 with ipilimumab + nivolumab, and 1 with nivolumab + relatlimab. Clinical trial information: NCT04645680 .