SCIB1 and iSCIB1+ in Melanoma Patients Receiving Nivolumab With Ipilimumab or SCIB1 With Pembrolizumab (The SCOPE Study)

Inclusion Criteria: 1. Histologically confirmed diagnosis of unresectable Stage III or Stage IV melanoma. 2. Not received prior systemic treatment for advanced disease. Prior neoadjuvant or adjuvant treatment, defined as treatment prior to or following resection of all detectable disease, is permitted; last dose must be at least 24 weeks before the first dose of SCIB1 or iSCIB1+. 3. Checkpoint inhibition with either nivolumab with ipilimumab or pembrolizumab will be an appropriate treatment for their advanced disease. 4. BRAF status must be known; patients with BRAF mutation positive disease may be enrolled without BRAF inhibitor treatment at the discretion of the Investigator, provided that they have no evidence of rapidly progressing disease. 5. At least one measurable lesion per RECIST 1.1 criteria by CT scan or MRI. 6. Human leukocyte antigen (HLA)-A2 positive (applicable for cohort 1, 2 and 3). 7. Positive for HLA-DR4, HLA-DR7, HLA-DR53 or HLA-DQ6 (applicable for cohort 1, 2 and 3). 8. Patients for whom nivolumab with ipilimumab is determined to be an appropriate treatment will be treated in cohort 4 with iSCIB1+ if: 1. the target HLA haplotype does not match as stated in criteria number 6 and 7, or 2. they are unable to wait for HLA screening results prior to enrolment or starting treatment, or 3. cohort 1 and cohort 3 have completed or closed to recruitment. 9. At least 18 years of age. 10. A life expectancy of more than 3 months. 11. ECOG performance status of 0 or 1. 12. Adequate organ function as determined by protocol laboratory values. 13. Able and willing to provide written informed consent prior to any study related procedure. 14. Women of child-bearing potential must have a negative serum pregnancy test during screening and be neither breastfeeding nor intending to become pregnant during study participation, and shall be warned of potential foetal harm from nivolumab with ipilimumab or pembrolizumab. Women of child-bearing potential must agree to use highly effective contraceptive methods prior to study entry, for the whole duration of study treatment, and for 120 days after discontinuation of SCIB1 or iSCIB1+, or nivolumab with ipilimumab, or pembrolizumab, whichever is last. 15. Men who are potentially fertile with partners of childbearing potential must agree to use highly effective contraceptive methods for the whole duration of study treatment, and for 120 days after discontinuation of SCIB1 or iSCIB1+, or nivolumab with ipilimumab, or pembrolizumab, whichever is last. 16. Must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures. Exclusion Criteria: 1. A diagnosis of mucosal, acral or ocular melanoma. 2. Has central nervous system metastases or carcinomatous meningitis. 3. Has previously received a treatment to block cytotoxic T lymphocyte associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), PD-L1, or programmed death-ligand 2 (PD-L2) with the following exception: patients who have received neoadjuvant or adjuvant treatment with these treatments are eligible, provided that the last dose was administered at least 24 weeks before the first dose of SCIB1 or iSCIB1+. 4. Patients with lactate dehydrogenase (LDH) \> 2 x ULN. 5. Expected to require any other form of systemic or localized anticancer therapy while receiving study treatment. 6. Taking any systemic steroid therapy within 1 week of the first dose of study drug or is receiving any other form of immune suppressant medication. Physiological doses of systemic steroids such as those for the management of adrenal insufficiency, as well as topical and inhaled steroids, such as those for the management of asthma, are permitted. 7. Receiving treatment with any investigational product within 28 days (or 5 half-lives of the treatment concerned) prior to the first dose of study treatment. 8. Has a previous (within 5 years) or current malignancy with the exception of melanoma, and curatively treated local tumours. 9. Has a concurrent illness which would preclude study conduct and assessment. 10. Has New York Heart Association class III or IV heart disease, myocardial infarction within previous 6 months, a heart rate of ≤ 50 beats per minute, a history of significant cardiac abnormality and/or clinically significant abnormal baseline ECG reading, active ischemia, or any other uncontrolled cardiac condition. 11. Has a history of severe hypersensitivity reaction to treatment with a monoclonal antibody. 12. Has an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents (patients with vitiligo or resolved childhood asthma/atopy are an exception and are not excluded for these conditions). The following patients are not excluded from the study: patients who require intermittent use of bronchodilators or local steroid injections, patients with hypothyroidism stable on hormone replacement, and patients who receive physiological doses of steroids as replacement therapy, such as those for the management of adrenal insufficiency. In such cases the recruiting investigator should discuss the patients' eligibility with the study Medical Monitor prior to enrolment. 13. Received a live vaccine within the 28 days prior to first dose of study treatment, or patient has received a non-live vaccine, including COVID-19 vaccines, within 14 days prior to first dose of study treatment. 14. A known history of human immunodeficiency virus (HIV) or has any positive test for hepatitis B virus or hepatitis C virus indicating active acute or chronic infection. 15. A known current or recent history (within the last year) of substance abuse including illicit drugs or alcohol.