Clinical outcomes of the DIET study: A randomized controlled phase 2 trial of a high fiber diet intervention (HFDI) in patients with melanoma receiving immune checkpoint blockade (ICB).

9511 Background: Dietary fiber intake is associated with response to ICB in melanoma. HFDIs favorably modulate the microbiome in non-cancer populations and in preclinical models. However, whether diet intervention can favorably modulate the microbiome and immune response in cancer patients is unknown. We conducted a proof-of-principal randomized trial of a fully controlled feeding study comparing HFDI with healthy control diet in melanoma patients receiving ICB. The primary objective was to establish the effects of HFDI on the structure and function of the gut microbiome. Here we report an exploratory objective of cancer-specific outcomes by arm. Methods: Patients initiating ICB treatment for melanomawere randomized (2:1) to either HFDI (30 g/d fiber ramped-up biweekly via whole foods to 50 g/d) or healthy control diet (20 g/d fiber). Diets in both arms met cancer prevention guidelines, were isocaloric and macronutrient-controlled, such that participants were provided all calorie-containing meals/snacks and met weekly with the dietitian for the study duration (up to 10 weeks). Objective response rate (ORR, per RECIST 1.1), pathological response rate (per INMC), progression-free survival (PFS), event-free survival (EFS, defined as the time from treatment initiation to disease progression, recurrence or death), recurrence rate (RR), recurrence-free survival (RFS) and immune-related adverse event (IRAE) rates were assessed and compared across arms. Results: 45 patients were randomized, of which 43 (F/M 22/21, median age 57 years, 79% cutaneous) initiated ICB and diet intervention: 28 in the HFDI arm and 15 in the control arm. ICB was administered in adjuvant, neoadjuvant and unresectable setting in 19, 12, and 12 patients, respectively. ICB regimens include pembrolizumab or nivolumab monotherapy (n = 19), ipilimumab + nivo (n = 16), and nivo + relatlimab (n = 7). At the time of data cut-off, October 2024, the median follow-up was 22.6 months (95% CI: 22.05-24.95 months). In the combined neoadjuvant/unresectable cohort (n = 24), ORR was 77% (HFDI) and 29% (control, p = 0.06). In the neoadjuvant cohort (n = 12), pathological complete response rate was 57%(HFDI) vs 50% (control, p = 1.0). Median EFS was not reached (HFDI) versus 20 months (control, p = 0.03). In the adjuvant cohort (n = 19), at a median follow-up of 27.6 months, RR was 14% (HFDI) versus 33% (control, p = 0.56). Median RFS was not reached (HFDI) versus 27.8 months (control, p = 0.49). Any grade IRAEs were observed in 71.4% of the patients in the HFDI arm versus 93.3% in the control arm (p = 0.13). Grade ≥3 IRAE rates were 28.6% and 40.0% in the HFDI and control arms (p = 0.51), respectively. Conclusions: Our study suggests potential benefits of HFDI on clinical outcomes and toxicity profile with ICB, warranting further study in Phase III trials powered for disease outcomes. Clinical trial information: NCT04645680 .