Impact of a Prebiotic Food-enriched Diet (PreFED) in Combination With Ipilimumab/Nivolumab Combination Immune Checkpoint Blockade (ICB) in ICB-refractory Melanoma Patients

Primary Objectives Determining the overall response rate (ORR) to PreFED intervention + Ipi/Nivo in ICB-refractory metastatic melanoma participants.

Secondary Objectives

• Determine progression-free survival (PFS) and overall survival (OS) to PreFED + Ipi/Nivo in ICB refractory melanoma
• Compliance and adherence to interventions
• Determine the safety (AEs) and tolerability (GSRS-IBS) of the dietary intervention
• Assess the rate of immune related adverse events in participants on immunotherapy receiving dietary interventions
• Assess the effects of dietary intervention on systemic and tumor immunity
• Assess the effect of dietary intervention on gut microbiome composition and networks
• Assess the effects of dietary intervention on gut metabolic output and systemic metabolism
• Assess the effects of dietary interventions on quality of life and other participant reported outcomes (PROs)

Inclusion criteria

• Age ≥ 18 years old
• English-speaking
• Body mass index (BMI) 18.5-45 kg/m2
• ECOG performance status of 0 or 1
• Histologically confirmed stage III/IV, unresectable cutaneous melanoma. Asymptomatic brain metastases are allowed.
• Prior treatment with anti-PD1 or anti-PD-1 + anti-LAG3 agents and documented disease progression either while on these agents or after stopping therapy without intervening therapy.
• Planned initiation of standard-of-care Ipilimumab 3 mg/kg + Nivolumab 1 mg/kg
• Measurable disease per RECIST 1.1
• Self-reported willingness to eat the provided foods (with some tailoring to their food preferences)
• Self-reported willingness to comply with scheduled visits, undergo venipuncture, provide stool samples.

Exclusion criteria

• Prior treatment with anti-CTLA4
• Mucosal or uveal melanoma
• Concurrent malignancy requiring systemic therapy other than hormonal therapy.
• History of inflammatory bowel disease, total colectomy, or bariatric surgery
• Currently taking steroids > Prednisone 10 mg/day or equivalent
• IV antibiotic use in the past month or oral antibiotic use in past 2 weeks
• Regularly taking supplements containing prebiotics, fiber and/or probiotics, and unable/unwilling to discontinue for the purpose of the study.
• Medical contraindications to the Intervention Diet as determined by the treating physician.
• Self-reported major dietary restrictions, including but not limited to relevant food allergies, celiac disease, or diets such as vegan, ketogenic, extended fasting.
• Insulin-dependent diabetes or conditions requiring bile-acid sequestrants.
• Current smoker or heavy drinker (defined as >14 drinks per week) or current illicit drug use.
• Currently pregnant, planning to become pregnant, or lactating.
• Cognitively impaired adults