Abstract CT245: Neoadjuvant immune checkpoint blockade + a prebiotic food-enriched dietary intervention to optimize immune response in melanoma: NEO-PreFED

Abstract

Abstract Background: Immune checkpoint blockade (ICB) has revolutionized the treatment of many cancers. However, not all patients respond, and immune-related toxicities remain a major challenge. We and others have shown that the gut microbiome is associated with response to ICB in melanoma patients and have functionally confirmed this association in pre-clinical models. Prebiotic foods, high in dietary fiber and other key nutrients, selectively support beneficial gut microbes and microbiota-derived metabolites underlying a favorable immune response to ICB. As such, accessible prebiotic foods hold strong potential as a safe, effective, and scalable strategy to augment the gut microbiota and immune response as an adjunct to ICB. We are conducting a single arm neoadjuvant study to increase patients’ intake of prebiotic foods together with ICB treatment in patients with high-risk, resectable melanoma. The central hypothesis is that administration of a Prebiotic Food-Enriched Diet (PreFED) intervention in combination with ICB is safe and will enhance the anti-tumor immune response. Methods: 35 melanoma patients (Stage IIIB-IV) starting neoadjuvant combination ICB therapy (ipilimumab/nivolumab or nivolumab/relatlimab) will be enrolled to the phase II PreFED intervention study (NCT06548789). PreFED intervention includes food provision of prebiotic snack packouts with diet counseling during neoadjuvant ICB. Following surgery, supportive diet counseling without food provision will be continued for an additional 8 weeks. Key inclusion criteria include planned initiation of neoadjuvant combination ICB, BMI 18.5-45 kg/m2, and willingness to eat the provided daily prebiotic foods. Key exclusion criteria include uveal melanoma, diabetes mellitus, inflammatory bowel disease, total colectomy or bariatric surgery, steroid or antibiotic use within 14 days, current smoker or heavy drinker, and regularly taking prebiotics or fiber supplements. In the neoadjuvant period prior to surgery, participants will receive two to three fully prepared prebiotic snacks per day and weekly diet counseling to support increased consumption of prebiotic foods. Participants will complete provided food logs to track compliance. Following surgery, participants who have not had progression or changed treatment will continue the supportive diet counseling (only) for 8 weeks. Blood and stool samples are collected longitudinally. Tumor tissue will be collected at baseline and surgery. The primary endpoint is to determine the feasibility of, compliance and adherence to PreFED intervention. Secondary endpoints include safety and tolerability of the PreFED intervention, objective response rate, pathological response rate, event-free survival and overall survival. A total of three patients have been enrolled to date, with two receiving ipilimumab/nivolumab and one receiving nivolumab/relatlimab. Citation Format: Yan Jiang, Rachel M. Farias, Cindy Hwang, Erma Levy, Jared Malk, Brenna Matejka, Yufan Qiu, Virginia Honaker, Elizabeth M. Burton, Christine Peterson, Nadim Ajami, Rodabe N. Amaria, Michael A. Davies, Adi Diab, Alexandra P. Ikeguchi, Isabella C. Glitza Oliva, Hussein A. Tawbi, Jennifer A. Wargo, Carrie R. Daniel, Jennifer L. McQuade. Neoadjuvant immune checkpoint blockade + a prebiotic food-enriched dietary intervention to optimize immune response in melanoma: NEO-PreFED [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT245.