This clinical trial aims to evaluate whether a ketogenic diet (KD), when combined with immunotherapy, can improve immune function and treatment outcomes in patients with advanced melanoma, cutaneous squamous cell carcinoma (cSCC), or renal cell carcinoma (RCC).

Why Is This Study Important? Immunotherapy is a promising cancer treatment, but not all patients respond well. Research suggests that diet, particularly a high-fat, low-carbohydrate ketogenic diet, may help boost the immune system and make treatments more effective.

What Will This Study Examine?

Researchers want to understand:

Is the ketogenic diet well-tolerated for cancer patients? Does the diet improve immune responses and treatment effectiveness?

How Will the Study Work?

Participants will be placed into one of two groups:

Ketogenic Diet (KD) Group: A structured high-fat, low-carb diet (intermittent schedule: 2 weeks on, 1 week off).

Standard Diet (SD) Group: A typical diet with no major changes. Throughout the study, a dietitian will closely support and guide you. Both groups will continue their standard immunotherapy treatment.

What Will Participants Do? Write their food intake three times a week to help assess dietary adherence Follow their assigned diet for 10 weeks Have weekly check-ins with a dietitian (in-person at the hospital or via phone) Have weekly blood glucose and ketone level checks using a home device. Provide monthly blood samples to measure immune response during routine immunotherapy infusions Provide stool samples for gut microbiome analysis at the start and end of the study Measure Monthly Weight, body composition, and resting calorie burn Complete quality-of-life questionnaires

What Are the Potential Benefits? Improved response to immunotherapy Better understanding of how diet influences cancer treatment Potential for a new supportive strategy for cancer care

This study may help uncover ways to enhance cancer treatment through personalized nutrition.

Inclusion Criteria:

• • Males and females, age >= 18 years

  • Patients with a histologically confirmed melanoma or cSCC or RCC receiving first line treatment with combination nivolumab and ipilimumab /relatlimab or single agent ipilimumab, nivolumab, pembrolizumab, Cemiplimab.

  • Able to read, understand, and provide written informed consent

  • Willing and able to complete all study-specific procedures and visits

  • Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤2.

  • Blood tests:

    • Creatinine (Cr) < 1.5 mg/dL.
    • Magnesium normal range ( 1.5 -2,6 mg/dL)
    • Liver function tests (LFTs) 2.5x upper limit of normal (ULN).
    • Neutrophils ≥ 1,000/mm3, platelets ≥ 50,000/mm3, Hb>8 g/dL
    • Women of childbearing potential must have a negative β-HCG pregnancy test documented within 1 week of registration.

Exclusion Criteria:

• • Individuals < 18 years of age

  • Unable or unwilling to provide consent
  • Other active malignancy (other than adequately treated and cured basal or squamous cell skin cancer, curatively treated in situ disease, or any other cancer from which the patient has been disease free >=2 years)
  • Currently consuming a low-carbohydrate (< 130 g/day) or KD or done so in the last 6-months
  • Patients currently participating in an interventional or therapeutic clinical trial involving the use of active anti-cancer therapy.
  • Active autoimmune diseases requiring active Immune suppressive medications
  • Systemic steroid therapy, excluding for replacement due to adrenal insufficiency
  • Major surgery within last 3 months
  • BMI <18 or >35
  • Medical contraindications to the intervention diet as determined by the treating physician.
  • Self-reported major dietary restrictions related to the intervention such as irritable bowel syndrome (IBS).
  • Patients with a history or active eating disorder
  • Uncontrolled Diabetes mellitus or patients receiving insulin
  • Known diagnosis of HIV
  • Known active hepatitis B or hepatitis C
  • Known inborn errors of lipid metabolism
  • Sever or uncontrolled Hyperlipidemia (total cholesterol over 400 mg / dL, low-density lipoprotein (LDL) above 300 mg / dL, triglycerides over 500 mg / dl.).
  • Pregnant or lactating.
  • Patients who have undergone a transplant