Background: Obesity promotes a chronic inflammatory state that is associated with PC progression. ADT can cause significant side effects including weight gain, accumulation of body fat, insulin resistance, and an increased risk of diabetes and cardiovascular disease. A WFPBD has been shown to promote weight loss, decrease chronic inflammation, and shift gut microbial profiles to a microbiome that promotes insulin sensitivity. We hypothesize that a WFPBD and behavior intervention will promote weight loss and a reduction in adiposity in overweight/obese patients with PC on ADT and will decrease biomarkers of metabo-inflammation; and that a WFPBD, which is enriched in fiber, will modulate the fecal microbiota and metabolites, and alter study participants’ serum metabolome. Correlative studies will offer insight into the impact of nutrition on metabolic pathways that are known to be affected by PC, ADT and/or excess body fat, including steroid metabolism, ketogenesis, and fatty acid metabolism. Methods: Key eligibility criteria include pts with PC with a BMI ≥ 27 receiving ADT with an LHRH/GnRH analogue for >24 weeks pre-study (+ androgen receptor pathway inhibitor for >3 mos) with anticipation of >26 more weeks of ADT. 60 patients randomized 1:1 between two cohorts. Cohort 1: pts receive 12 prepared meals (provided by Plantable) per weeks 1-4 and 6 meals weeks 5-8 plus Plantable coaching, nutritional counseling and education to assist in self-prepping plant-based meals (weeks 9-26); Cohort 2 (control): pts receive general nutritional counseling from a Registered Dietician weekly for 8 weeks, then monthly x 4. Collection of baseline and serial measurements (pre-intervention, weeks 4, 8 and 26) including weight, serum carotenoid levels (to monitor dietary compliance), dual energy x-ray absorptiometry (DXA) scans, MnSOD polymorphisms, and biomarkers of inflammation and metabolism. The primary comparison is weight loss at 4 weeks (with an 80% power to detect an effect size 0.74 standard deviations with a 2-sided significance level of 0.05 using a two-sample t-test). Secondary objectives will assess and compare changes in: a) biomarkers of metabolic disorders (Hemoglobin A1c, fasting insulin/glucose) and cardiovascular risk (LDL cholesterol, HDL cholesterol, triglycerides); b) pro-inflammatory markers (IL-6, hsCRP) and adipokines (leptin, adiponectin); c) fecal microbiota; and d) quality of life measurements. Exploratory objectives will assess the effects of a WFPBD on serum and fecal metabolomics and on clonal hematopoiesis. Trial is open at Weill Cornell Medicine (WCM), John Hopkins University and Columbia University. First pt enrolled at WCM September 2022. Funding support from the Prostate Cancer Foundation; PC Clinical Trials Consortium c22-301. Clinical trial information: NCT05471414.