This is a randomized, double-blind, fully controlled feeding study that will enroll melanoma patients starting standard-of-care ICB in three settings: adjuvant, neoadjuvant, and unresectable. Patients are randomized to the high fiber or healthy control diet. The goal of the study is to establish the effects of dietary intervention on the structure and function of the gut microbiome in patients with melanoma treated with SOC immunotherapies.

PRIMARY OBJECTIVE:

To establish the effects of dietary intervention on the structure and function of the gut microbiome.

SECONDARY OBJECTIVES:

1. Assess the effects of dietary intervention on gut metabolic output and systemic metabolism.
2. Assess the effects of dietary intervention on systemic and tumor immunity
3. Determine the safety (AEs) and tolerability (GSRS-IBS) of the dietary intervention
4. Assess the rate of immune related adverse events in patients on immunotherapy receiving dietary interventions
5. Determine the maximum daily fiber content that 70% of participants are able to tolerate
6. Assess the adherence to the dietary interventions as defined by 70% of calories consumed over the duration of the study being derived from provided diets (as measured by food records)
7. Assess the effects of dietary interventions on quality of life and other patient reported outcomes (PROs)

EXPLORATORY OBJECTIVES:

1. Assess the association of dietary interventions with clinical outcomes (objective response rate [ORR] and progression-free survival [PFS] rate in unresectable cohort and recurrence rate [RR] in adjuvant cohort).
2. Explore predictors of biological response to dietary interventions.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I (ISOCALORIC HIGH-FIBER DIET): Patients receive a whole foods diet that follows the recommended American Cancer Society guidelines but is higher in fiber for 11 weeks.

ARM II (ISOCALORIC CONTROL DIET): Patients receive a standard whole foods diet of recommended by the American Cancer Society for 11 weeks.

After completion of study, patients are followed up at 12 weeks.

Inclusion Criteria:

1. Age ≥ 18 years old.

2. Body mass index (BMI) 18.5-40 kg/m^2

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

4. English-speaking

5. Self-reported willingness to exclusively eat the provided diets

6. Self-reported willingness to comply with scheduled visits, undergo venipuncture, and provide stool samples

7. Cohort-specific:

   • 1 Adjuvant Melanoma: i. Resected Stage II-IV melanoma with planned initiation of adjuvant anti-PD1 +/- anti-CTLA4 or anti-LAG3
   • 2 Unresectable Melanoma: i. Histologically confirmed unresectable stage III or Stage IV melanoma with planned initiation of standard of care anti-PD1 +/- CTLA4 or anti-PD1 +/- LAG3 immunotherapy and no prior immunotherapy in the metastatic setting.
   • 3 Neoadjuvant Melanoma: i. Histologically confirmed stage III/IV melanoma with planned initiation of neoadjuvant anti-PD1 +/- anti-CTLA4 or anti-LAG3 1. Participants must have archival tissue block available or be willing to undergo a newly-obtained core needle or incisional biopsy at baseline. Fine needle aspiration is not acceptable.
   • 4 Unresectable RCC: i. Unresectable clear-cell renal cell carcinoma with planned initiation of standard of care anti-PD1 +/- anti-CTLA4 immunotherapy

Exclusion Criteria:

1. History of >= grade II colitis or diarrhea on immunotherapy or any ongoing colitis or diarrhea of any grade
2. Unresolved >= grade III immune-related adverse event on immunotherapy (other than endocrinopathy requiring hormone replacement)
3. History of active inflammatory bowel disease or major gastrointestinal surgery (not including appendectomy or cholecystectomy) within 3 months of enrollment or any history of total colectomy, or bariatric surgery (bariatric surgery which does not disrupt the gastrointestinal lumen, i.e. restrictive procedures such as banding, are permitted).
4. Medical contraindications to intervention diet as determined by the treating physician
5. Self-reported major dietary restrictions related to the intervention
6. Diagnosis of diabetes mellitus type I or type II that requires medical treatment or random glucose > 200 mg/dL
7. Antibiotic use within 21 days of planned start of equilibration diet (self-reported and/or noted by the treating physician)
8. Has a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study intervention administration. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
9. Regularly taking probiotics, fiber supplements, or any other medication or supplement that could affect study outcome as determined by the principal investigator and unable/unwilling to discontinue for the purpose of the study. These agents must be discontinued at least 14 days prior to start of diet
10. Currently consuming an average estimated daily fiber intake exceeding 20 grams based on the results of the preliminary dietary assessment; vegetarian or vegan
11. Current smoker or heavy drinker (defined as > 14 drinks per week) or current self reported illicit drug use
12. Uncontrolled concurrent illness or infection or psychiatric illness/social situations that would limit compliance with study requirements
13. Unable or unwilling to undergo study procedures
14. Plan for travel during the study that would preclude adherence to prescribed diets
15. Cognitively impaired adults

Participants will be blinded to their assigned diet throughout the intervention as will the investigators and research staff with the exception of the dietitian and the staff performing group assignment and data entry who will not have contact with participant