A Phase 2, Multicentre, Open-Label, Umbrella Study of SCIB1 and iSCIB1+ in Patients With Advanced Unresectable Melanoma Receiving Nivolumab With Ipilimumab or SCIB1 With Pembrolizumab (The SCOPE Study)
The purpose of this study is to find out if two new treatment cancer vaccines called SCIB1 and iSCIB1+ can be used safely when added to nivolumab (Opdivo) with ipilimumab (Yervoy), or SCIB1 with pembrolizumab (Keytruda). Pembrolizumab or nivolumab with ipilimumab are standard treatments approved for patients with advanced melanoma (skin cancer). The study will also look to see if SCIB1 or iSCIB1+ can increase the likelihood that melanoma patients will respond to the standard treatments, and also if SCIB1 and iSCIB1+ can help to make those responses last longer. SCIB1 and iSCIB1+ are considered experimental. SCIB1 has been given to melanoma patients in an earlier study. It was generally well-tolerated, and researchers saw some signs that it may help to stimulate the immune system, which is a way in which the body can fight the cancer. iSCIB1+ is similar to SCIB1 but might benefit more patients with melanoma.
• Histologically confirmed diagnosis of unresectable Stage III or Stage IV melanoma.
• 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+.
• Checkpoint inhibition with either nivolumab with ipilimumab or pembrolizumab will be an appropriate treatment for their advanced disease.
• 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.
• At least one measurable lesion per RECIST 1.1 criteria by CT scan or MRI.
• Human leukocyte antigen (HLA)-A2 positive (applicable for cohort 1, 2 and 3).
• Positive for HLA-DR4, HLA-DR7, HLA-DR53 or HLA-DQ6 (applicable for cohort 1, 2 and 3).
• Patients for whom nivolumab with ipilimumab is determined to be an appropriate treatment will be treated in cohort 4 with iSCIB1+ if:
∙ the target HLA haplotype does not match as stated in criteria number 6 and 7, or
‣ they are unable to wait for HLA screening results prior to enrolment or starting treatment, or
‣ cohort 1 and cohort 3 have completed or closed to recruitment.
• At least 18 years of age.
⁃ A life expectancy of more than 3 months.
⁃ ECOG performance status of 0 or 1.
⁃ Adequate organ function as determined by protocol laboratory values.
⁃ Able and willing to provide written informed consent prior to any study related procedure.
⁃ 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.
⁃ 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.
⁃ Must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.