The SCOPE Study

Patients must meet the following criteria in order to be included in the study:

1) Patient has histologically confirmed, unresectable Stage III or Stage IV melanoma as defined by the American Joint Committee on Cancer (AJCC) (Gershenwald et al 2017).

2) Patient has not received prior systemic treatment for advanced disease. Prior adjuvant treatment, defined as treatment following resection of all detectable disease, is permitted; last dose must be at least 4 weeks before the first dose of SCIB1.

3) Patient has been clinically evaluated and checkpoint inhibition with either nivolumab with ipilimumab or pembrolizumab has been determined to be an appropriate treatment for their advanced disease.

4) Patient’s 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 (lactate dehydrogenase [LDH] above normal range, clinically significant tumour-related symptoms).

5) Patient has at least one measurable lesion per RECIST 1.1 criteria by computed tomography (CT) scan or magnetic resonance imaging (MRI).

6) Patient has an archival (< 5 years of age) or fresh biopsy sample of tumour available for analysis of programmed death-ligand 1 (PD-L1) expression .

7) Patient is HLA-A2 positive.*

8) Patient is positive for HLA-DR4, HLA-DR7, HLA-DR53 or HLA-DQ6.*

9) Patient is at least 18 years of age.

10) Patient has a life expectancy of more than 3 months.

11) Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

12) Patient has adequate organ function as determined by the protocol laboratory values. 13) Patient must be able and willing to provide written REC-approved informed consent prior to any study-related procedure. In the event that the patient is re-screened for study participation or if a protocol amendment alters the care of an ongoing patient, a new REC-approved informed consent form (ICF) must be signed.

14) Women of child-bearing potential (including women ≤ 12 months from last menstrual period) must have a negative serum pregnancy test during Screening (within the 72 hours before planned administration of the first dose of study drug on Day 1) and be neither breastfeeding nor intending to become pregnant during study participation, and shall be warned of potential foetal harm from either 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, 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, nivolumab with ipilimumab, or pembrolizumab, whichever is last.

16) Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

* HLA testing will be conducted at accredited laboratories by molecular (DNA) typing. 

Exclusion criteria:

A patient will not be eligible for the study if he/she meets one or more of the following criteria:

1) Patient has a diagnosis of mucosal, uveal or ocular melanoma. 2) Patient has active central nervous system metastases or carcinomatous meningitis (patients with a response to previous treatment for brain metastases are eligible provided that they are stable without MRI evidence of progression for at least 4 weeks prior to the first dose of study treatment, and systemic steroids have been withdrawn for at least 2 weeks).

3) Patient has previously received a treatment to block cytotoxic T lymphocyte (CTL)-associated protein 4 (CTLA-4), PD-1, PD-L1, or programmed death-ligand 2 (PD-L2) with the following exception: patients who have received adjuvant treatment with these treatments are eligible.

4) Patient is expected to require any other form of systemic or localised antineoplastic therapy while on study.

5) Patient is 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.

6) Patient is 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.

7) Patient has a previous (within 5 years) or current malignancy with the exception of melanoma, and curatively treated local tumours such as carcinoma-in-situ of the breast, cervix, basal or squamous cell carcinoma of the skin, prostate cancer with Gleason grade < 6 and prostate specific antigen within normal range.

8) Patient has a concurrent illness which would preclude study conduct and assessment, including, but not limited to uncontrolled medical conditions, uncontrolled and active infection (considered opportunistic, life threatening, or clinically significant), uncontrolled risk of bleeding, or uncontrolled diabetes mellitus, or pulmonary disease (including obstructive pulmonary disease, pulmonary fibrosis, and history of symptomatic bronchospasm), or alcoholic liver disease, or primary biliary cirrhosis. Caution should be used for patients with suspected or diagnosed epilepsy.

9) Patient has New York Heart Association (NYHA) 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 ischaemia, or any other uncontrolled cardiac condition such as angina pectoris, clinically significant arrhythmia requiring therapy including anticoagulants, uncontrolled hypertension (> 140/90 mm Hg), significant cerebrovascular disease, or congestive heart failure.

10) Patient has a history of severe hypersensitivity reaction to treatment with a mAb.

11) Patient 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.

12) Patient has received a vaccine within 28 days of first dose of study treatment.

13) Patient has a known history of human immunodeficiency virus (HIV), or has any positive test for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating active acute or chronic infection.

14) Patient has a known current or recent history (within the last year) of substance abuse including illicit drugs or alcohol. 

Research Nurse: Carolyn Hatch (x3921) Carolyn.Hatch@lthtr.nhs.uk

Administrator: Bethany Webster (x8475)