This study is open to patients with a type of cancer called melanoma. Patients can join the study if their tumor cannot be removed by surgery or has spread to other organs, and are planned to receive immunotherapy as treatment for their cancer. This study is looking at whether taking calcium pantothenate supplement (a type of Vitamin B5) can increase its levels in the blood and have an effect in the immune system, when its used in combination with the immunotherapy.

This single-center, single-cohort study aims to investigate the effectiveness of oral calcium pantothenate (C-PAN) in raising plasma pantothenic acid levels in melanoma patients. Conducted at Princess Margaret Cancer Centre, the study will enroll 12 eligible subjects with locally unresectable or metastatic melanoma undergoing first-line standard of care (SOC) with combined immune checkpoint inhibitor (ICI) therapy, Nivolumab and Ipilimumab. Additionally, the study will explore changes in immune cell subsets, metabolomics, and gut microbiome to understand the impact of pantothenate/CoA pathway manipulation on ICI efficacy and immune-mediated colitis prevention.

Patients will initially receive a run-in period of C-PAN at a dose of 2000 mg daily for 3 to 7 days, alongside approved SOC drugs. Subsequently, patients will continue with the maintenance dose of 2000 mg daily, starting on the same day as the first cycle of combined ICI. This maintenance dose will be continued until the occurrence of unacceptable toxicity, disease progression by iRECIST criteria, or for a maximum duration of 1 year, whichever comes first, unless there are specific criteria indicating the discontinuation of C-PAN.

For all subjects, radiologic imaging to assess response to treatment will be performed as per standard practice (ideally every 8 to 12 weeks, with first assessment at week 9). Fecal samples will be collected from all subjects at baseline (1st sample), at week 9 following the start of ICI, and at study completion or discontinuation. An additional fecal sample will be collected in case of development of immune-related colitis or immune-related diarrhea.

Standard laboratory investigations for immunotherapy will be collected as per institutional practice. Blood samples for biomarkers will be collected at various time points.

Inclusion Criteria:

• 1. Signed written and voluntary informed consent.
• 2. Age ≥18 years, male or female.
• 3. Have histologically or cytological documented unresectable stage III or stage IV metastatic melanoma (AJCC 8th edition).
• 4. Have not received any previous systemic treatment for advanced melanoma, including chemotherapy, immunotherapy or targeted therapy.
• 5. Be willing and able to provide stool and blood specimen for analyses at protocol specified time points.
• 6. Performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) performance scale.
• 7. Not pregnant for females of child bearing potential as indicated by negative serum or urine pregnancy test within 72 hours of study start

Exclusion Criteria:

• 1. Subjects unable to swallow orally administered medications or any subjects with gastrointestinal disorders likely to interfere with absorption (e.g. bowel obstruction, short gut syndrome, blind loop syndrome, ileostomy, etc.). Subjects with colostomies may be enrolled.
• 2. Subjects with inflammatory bowel disease.
• 3. Any condition that, in the opinion of the Investigator, would interfere with subject safety, or evaluation of the collected specimen and interpretation of study result.
• 4. Pregnant or planning to get pregnant in the next 6 months.
• 5. Female patient breastfeeding.
• 6. Allergy to the investigational product (or its non-medicinal ingredients)- Calcium Pantothenate (stearic acid, Hydroxypropyl methylcellulose) or Immune checkpoint inhibitors (or its non-medicinal ingredients)- Nivolumab (Hydrochloric acid, mannitol (E421), pentetic acid, polysorbate 80, sodium chloride, sodium citrate, sodium hydroxide) and Ipilimumab (diethylene triamine pentaacetic acid (DTPA), mannitol, polysorbate 80, sodium chloride, Tris-hydrochloride, sodium hydroxide, hydrochloric acid