SCIB1 in Melanoma Patients Receiving Either Nivolumab With Ipilimumab or Pembrolizumab (The SCOPE Study)

Study Overview
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Brief Summary
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The purpose of this study is to find out if a new treatment cancer vaccine called SCIB1 can be used safely when added to either nivolumab (Opdivo) with ipilimumab (Yervoy) or pembrolizumab (Keytruda), standard treatments approved for patients with advanced melanoma (skin cancer). The study will also look to see if SCIB1 can increase the likelihood that melanoma patients will respond to either nivolumab with ipilimumab or pembrolizumab, and also if SCIB1 can help to make those responses last longer. SCIB1 is 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.

Detailed Description
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This is an open label, single arm Phase 2 study to determine the safety and tolerability of intramuscular SCIB1 when added to either nivolumab (Opdivo) with ipilimumab (Yervoy) or pembrolizumab (Keytruda), standard treatments already approved for the treatment of advanced melanoma. The plan for this study is for SCIB1 to be given up to 10 times for 85 weeks, in combination with either nivolumab with ipilimumab or pembrolizumab according to the current label. The SCIB1 injection will be given using PharmaJet Stratis® needle-free injection device system in the upper arm or upper leg. Before treatment starts and after consent has been given, all patients will undergo screening tests (to be completed within 28 days of treatment initiation) to ensure the patient is eligible to take part. Over the 85-week treatment period, the patient will visit the hospital multiple times and have some telephone/video calls. The evaluations and procedures that will be carried out at each visit are all detailed in the study information sheets given to the patient before consent is taken. In response to the COVID-19 pandemic, the treatment burden for patients has also been reduced where possible by conducting remote assessments via telephone or video conference.

Official Title
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A Phase 2, Multicentre, Open-Label Study of SCIB1 in Patients With Advanced Unresectable Melanoma Receiving Either Nivolumab With Ipilimumab or Pembrolizumab (The SCOPE Study)

Conditions
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Malignant Melanoma, Melanoma (Skin), Melanoma Stage III, Melanoma Stage IV

Intervention / Treatment
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* Biological: SCIB1 DNA vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of unresectable Stage III or Stage IV melanoma. 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. 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. Positive for HLA-DR4, HLA-DR7, HLA-DR53 or HLA-DQ6. At least 18 years of age. A life expectancy of more than 3 months. An 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 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 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. Exclusion Criteria: A diagnosis of mucosal or ocular melanoma. 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). 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 adjuvant treatment with these treatments are eligible. Expected to require any other form of systemic or localized anticancer therapy while receiving study treatment. 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. 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. Has a previous (within 5 years) or current malignancy with the exception of melanoma, and curatively treated local tumours. Has a concurrent illness which would preclude study conduct and assessment. 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. Has a history of severe hypersensitivity reaction to treatment with a monoclonal antibody. 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. Received a vaccine within the 28 days prior to first dose of study treatment. 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. A known current or recent history (within the last year) of substance abuse including illicit drugs or alcohol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open label, uncontrolled study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SCIB1<br>SCIB1 administered by intramuscular needle-free injection | Biological: SCIB1 DNA vaccine<br>* The plan for this research study is for SCIB1 to be given for up to 85 weeks, in combination with either nivolumab with ipilimumab or pembrolizumab according to the current label. After receiving the first dose of SCIB1, the patient will receive SCIB1 at 4, 7, 13 and 25 weeks, then every 12 weeks up to Week 85. Nivolumab with ipilimumab or pembrolizumab treatment will be started 1 week after the first dose of SCIB1 and given as per standard treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of SCIB1 in participants receiving either nivolumab with ipilimumab or pembrolizumab assessed by the evaluation of adverse events (AEs) and the use of concomitant medications (Run-In Sub-Cohorts) | National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events; CTCAE v5.0. | From enrolment through last recorded assessment of safety, 2 years (Week 97) from the first dose of study drug | 
| Safety and tolerability of SCIB1 in participants receiving either nivolumab with ipilimumab or pembrolizumab assessed by the evaluation of vital signs, physical examination, 12-lead ECG, laboratory assessments and performance status (Run-In Sub-Cohorts) | Safety will be summarised for vital signs [temperature (°C).; pulse (beats per minute); respiratory rate (breaths per minute); systolic and diastolic blood pressure (mm Hg)]; physical examination of the participant (binary classification: normal or abnormal); 12-lead ECG (ECG abnormalities will be reported as an AE); laboratory assessments and grading of performance status as defined by the European Cooperative Group (ECOG) Performance Status score on a 6-point scale. | From enrolment through end of treatment (28 days after the final dose of study treatment) | 
| Safety and tolerability of SCIB1 in participants receiving either nivolumab with ipilimumab or pembrolizumab assessed by the injection site reaction (Run-In Sub-Cohorts) | Clinician assessment of the injection site reaction using a 3-point scale where 1 = 'mild' and 3 = 'severe'. | From the first dose of study drug to last post-study drug assessment (3 weeks after the last dose of study drug | 
| Objective response rate (ORR) of SCIB1 in patients receiving either nivolumab with ipilimumab or pembrolizumab relative to historical data for the nivolumab with ipilimumab combination or pembrolizumab alone in this patient population (Main Study) | ORR assessed by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) criteria. | From enrolment through last recorded assessment of response, up to 2 years (Week 97) from the first dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response of SCIB1 in patients receiving either nivolumab with ipilimumab or pembrolizumab relative to historical data for the nivolumab with ipilimumab combination or pembrolizumab alone in this patient population (Main Study) | Duration of response, measured from the point of first response (complete response or partial response) to the date of disease progression (per RECIST 1.1) or death due to any cause. | From enrolment through last recorded assessment of response, up to 2 years (Week 97) from the first dose of study drug | 
| ORR assessed by the modified RECIST 1.1 for immune-based therapeutics (iRECIST) (Main Study) | ORR assessed by iRECIST criteria. | From enrollment through last recorded assessment of response, up to 2 years (Week 97) from the first dose of study drug | 
| Progression Free Survival (PFS) rate. | PFS rate is defined as the proportion of participants who have not progressed (per RECIST 1.1 and iRECIST), or started new anticancer therapy, or died. | At 1 year (Week 49) and 2 years (Week 97) from the first dose of study drug | 
| Overall survival (OS) rate. | OS rate is defined as the proportion of participants who remain alive. | At 1 year (Week 49) and 2 years (Week 97) from the first dose of study drug | 
| Safety and tolerability of SCIB1 in participants receiving either nivolumab with ipilimumab or pembrolizumab assessed by the evaluation of AEs and the use of concomitant medications (Main Study) | [NCI] CTCAE v5.0. | From enrolment through last recorded assessment of safety, 2 years (Week 97) from the first dose of study drug | 
| Safety and tolerability of SCIB1 in participants receiving either nivolumab with ipilimumab or pembrolizumab assessed by the evaluation of vital signs, physical examination, 12-lead ECG, laboratory assessments and performance status (Main Study) | Safety will be summarised for vital signs [temperature (°C); pulse (beats per minute); respiratory rate (breaths per minute); systolic and diastolic blood pressure (mm Hg)]; physical examination of the participant (binary classification: normal or abnormal); 12-lead ECG (ECG abnormalities will be reported as an AE); laboratory assessments and grading of performance status as defined by the European Cooperative Group (ECOG) Performance Status score on a 6-point scale. | From enrolment through end of treatment (28 days after the final dose of study treatment) | 
| Safety and tolerability of SCIB1 in participants receiving either nivolumab with ipilimumab or pembrolizumab assessed by the injection site reaction (Main Study) | Clinician assessment of the injection site reaction using a 3-point scale where 1 = 'mild' and 3 = 'severe'. | From the first dose of study drug to last post-study drug assessment (3 weeks after the last dose of study drug) |