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

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.

Study Overview

• Status: Recruiting
• Conditions: Melanoma (Skin); Malignant Melanoma; Melanoma Stage IV; Melanoma Stage III
• Intervention / Treatment: Biological: SCIB1 or iSCIB1+ DNA vaccine

Detailed Description

This is an open label, single arm Phase 2 study to determine the response rate and safety and tolerability of intramuscular SCIB1 or iSCIB1+ when added to nivolumab (Opdivo) with ipilimumab (Yervoy) or SCIB1 with pembrolizumab (Keytruda). Pembrolizumab or nivolumab with ipilimumab are standard treatments already approved for the treatment of advanced melanoma.

The plan for this study is for SCIB1 or iSCIB1+ to be given up to 10 times for 85 weeks, in combination with nivolumab with ipilimumab or SCIB1 with pembrolizumab. The standard treatments will be given according to the current label. The SCIB1 or iSCIB1+ 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.

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Robert Miller; Phone Number: +44 (0)1865 582 690; Email: info@scancell.co.uk

Study Locations

• United Kingdom
  • Cambridge, United Kingdom
    • Recruiting
    • Cambridge University Hospitals NHS Foundation Trust
    • Contact: Pippa Corrie, MD
    • Principal Investigator: Pippa Corrie, MD
  • Cardiff, United Kingdom
    • Recruiting
    • Velindre University NHS Trust
    • Contact: Satish Kumar, MD
    • Principal Investigator: Satish Kumar, MD
  • Leeds, United Kingdom
    • Recruiting
    • The Leeds Teaching Hospitals NHS Trust
    • Contact: Maria Marples, MD
    • Principal Investigator: Maria Marples, MD
  • London, United Kingdom
    • Recruiting
    • The Royal Marsden NHS Foundation Trust
    • Contact: Kate Young, MD
    • Principal Investigator: Kate Young, MD
  • London, United Kingdom
    • Recruiting
    • Royal Free London NHS Foundation Trust
    • Contact: Amna Sheri, MD
    • Principal Investigator: Amna Sheri, MD
  • London, United Kingdom
    • Recruiting
    • Guy's & St Thomas' NHS Foundation Trust
    • Contact: Amanda Fitzpatrick, MD
    • Principal Investigator: Amanda Fitzpatrick, MD
  • Manchester, United Kingdom
    • Not yet recruiting
    • The Christie NHS Foundation Trust
    • Contact: Rebecca Lee, MD
    • Principal Investigator: Rebecca Lee, MD
  • Northwood, United Kingdom
    • Recruiting
    • East and North Hertfordshire NHS Trust
    • Contact: Heather Shaw, MD
    • Principal Investigator: Heather Shaw, MD
  • Nottingham, United Kingdom
    • Recruiting
    • Nottingham University Hospitals NHS Trust
    • Contact: Poulam M Patel, MD
    • Principal Investigator: Poulam M Patel, MD
  • Oxford, United Kingdom
    • Recruiting
    • Oxford University Hospital NHS Foundation Trust
    • Contact: Miranda Payne, MD
    • Principal Investigator: Miranda Payne, MD
  • Plymouth, United Kingdom
    • Recruiting
    • University Hospital Plymouth NHS Trust
    • Contact: Hannah Simonds, MD
    • Principal Investigator: Hannah Simonds, MD
  • Preston, United Kingdom
    • Recruiting
    • Lancashire Teaching Hospitals NHS Foundation Trust
    • Contact: Kellati Prasad, MD
    • Principal Investigator: Kellati Prasad, MD
  • Sheffield, United Kingdom
    • Recruiting
    • Sheffield Teaching Hospital NHS Foundation Trust
    • Contact: Sarah Danson, MD
    • Principal Investigator: Sarah Danson, MD
  • Southampton, United Kingdom
    • Recruiting
    • University Hospital Southampton NHS Foundation Trust
    • Contact: Ioannis Karydis, MD
    • Principal Investigator: Ioannis Karydis, MD
  • Taunton, United Kingdom
    • Recruiting
    • Somerset NHS Foundation Trust
    • Contact: Clare Barlow, MD
    • Principal Investigator: Clare Barlow, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 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 for SCIB1 administration (cohort 1 and 2).
• Positive for HLA-DR4, HLA-DR7, HLA-DR53 or HLA-DQ6 for SCIB1 administration (cohort 1 and 2).

• Patients for whom nivolumab with ipilimumab is determined to be an appropriate treatment will be treated in cohort 3 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 has completed recruitment.
• 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 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.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SCIB1 or iSCIB1+; SCIB1 or iSCIB1+ administered by intramuscular needle-free injection	Biological: SCIB1 or iSCIB1+ DNA vaccine; Participants receive up to 10 doses of either SCIB1 or iSCIB1+ up to 85 weeks, in combination with nivolumab with ipilimumab or SCIB1 with pembrolizumab. Nivolumab with ipilimumab or pembrolizumab treatment will be started 1 week after the first dose of SCIB1 or iSCIB1+ and given as per standard treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability assessed by the evaluation of adverse events (AEs) (Run-In Sub-Cohorts)	National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events; CTCAE v5.0.	Up to 30 days after the final dose of study drug
Safety and tolerability assessed by the evaluation of vital signs, physical examination, 12-lead ECG, laboratory assessments, performance status, injection site reaction and the use of concomitant medications (Run-In Sub-Cohorts)		Up to 30 days after the final dose of study drug
Objective response rate (ORR) (Main Study)	ORR assessed by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) criteria.	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 (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.	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.	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.	Up to 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.	Up to 2 years (Week 97) from the first dose of study drug
Safety and tolerability by the evaluation of AEs (Main Study)	NCI CTCAE v5.0.	Up to 30 days after the final dose of study drug
Safety and tolerability by the evaluation of vital signs, physical examination, 12-lead ECG, laboratory assessments, performance status, injection site reaction and the use of concomitant medications (Main Study)		Up to 30 days after the final dose of study drug

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory: Immune response	Immune response as measured using ELISpot and other assays on peripheral blood samples from patients.	Up to 30 days after the final dose of study treatment
Exploratory: Marker expression	Analysis of tumour biopsy samples for various markers.	Up to 30 days after the final dose of study treatment

Collaborators and Investigators

• Sponsor: Scancell Ltd
• Investigators: Principal Investigator: Poulam Patel, University of Nottingham

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2019
• Primary Completion (Estimated): January 31, 2026
• Study Completion (Estimated): January 31, 2026

Study Registration Dates

• First Submitted: August 16, 2019
• First Submitted That Met QC Criteria: September 2, 2019
• First Posted (Actual): September 6, 2019

Study Record Updates

• Last Update Posted (Actual): June 24, 2024
• Last Update Submitted That Met QC Criteria: June 18, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma
• Other Study ID Numbers: SCIB1-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is not a plan to make IPD available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No