iSCIB1+ in Combination With Ipilimumab and Nivolumab as First-Line Treatment for Advanced Unresectable Melanoma

NCT07815574 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: SCIB1-003
• Study Type: interventional
• Target: 550
• Locations: 2 countries
• Sites: 2

Brief Summary

This Phase 3 clinical trial is evaluating whether adding iSCIB1+, an investigational DNA-based cancer vaccine, to standard immunotherapy with nivolumab and ipilimumab can improve outcomes for people with advanced unresectable melanoma. Participants will be randomly assigned to receive either iSCIB1+ or a placebo, in addition to standard treatment with nivolumab and ipilimumab. Neither participants nor study doctors will know which treatment has been assigned. The study will compare how long participants live without their cancer worsening, overall survival, tumor response, safety, and quality of life. iSCIB1+ is designed to stimulate the immune system to recognize and attack melanoma cells by targeting proteins commonly found on melanoma tumors. Earlier studies have shown encouraging signs of immune activation and anti-tumor activity when iSCIB1+ was combined with checkpoint inhibitor immunotherapy. This study aims to determine whether adding iSCIB1+ to standard immunotherapy provides additional benefit compared with standard immunotherapy alone

Conditions

Melanoma (Skin Cancer); Advanced Melanoma; Metastatic Melanoma; Skin Cancer

Keywords

Melanoma; advanced melanoma; cancer vaccine; skin cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Progression-free survival (PFS), defined as the time from randomization to the earliest occurrence of disease progression per RECIST v1.1 as assessed by Blinded Independent Central Review (BICR) or death from any cause.

  Up to 4 years after randomization.

Secondary Outcomes (9)

• Overall Survival (OS)

  Up to approximately 4 years months after randomization.

• Objective Response Rate (ORR)

  Up to 4 years after randomization.

• Duration of Response (DoR)

  Up to 4 years after randomization.

• Disease Control Rate (DCR)

  Up to 4 years after randomization.

• Incidence of Treatment-Emergent Adverse Events (TEAEs)

  From informed consent and up to 4 years from randomization

Other Outcomes (3)

• Immune Response to iSCIB1+: Change from baseline in antigen-specific T-cell response measured by IFN-γ ELISpot assay

  From informed consent and up to 4 years from randomization

• Change from baseline in exploratory tumor, blood, and immune biomarker levels

  From informed consent until completion of study participation (i.e. up to 4 years)

• Change from baseline in exploratory immune-related biomarker measurements

  From baseline and up to 4 years from day 1.

Study Arms (2)

iSCIB1+ in combination with Ipilimumab and Nivolumab

EXPERIMENTAL

Participants will receive iSCIB1+ in combination with standard immunotherapy consisting of nivolumab and ipilimumab. Treatment will be administered according to the protocol-defined dosing schedule. Following induction treatment with nivolumab and ipilimumab, participants will continue nivolumab maintenance therapy. This arm is designed to evaluate whether the addition of iSCIB1+ improves clinical outcomes compared with placebo when administered in combination with nivolumab and ipilimumab in participants with advanced unresectable melanoma.

Biological: iSCIB1+; Drug: Nivolumab & Ipilimumab

Placebo + Nivolumab and Ipilimumab

PLACEBO COMPARATOR

Participants will receive placebo in combination with standard immunotherapy consisting of nivolumab and ipilimumab. Treatment will be administered according to the protocol-defined dosing schedule. Following induction treatment with nivolumab and ipilimumab, participants will continue nivolumab maintenance therapy. This arm serves as the comparator for evaluating the efficacy and safety of iSCIB1+ when added to standard first-line immunotherapy in participants with advanced unresectable melanoma.

Drug: Nivolumab & Ipilimumab; Other: Placebo

Interventions

iSCIB1+ BIOLOGICAL

iSCIB1+ is a DNA-based therapeutic cancer vaccine designed to enhance T-cell immune responses against melanoma-associated antigens. The vaccine encodes epitopes derived from glycoprotein 100 (gp100) and tyrosinase-related protein 2 (TRP-2) that are delivered using Scancell's ImmunoBody® platform. In this study, iSCIB1+ is administered by intramuscular injection with electroporation in combination with nivolumab and ipilimumab for the treatment of advanced unresectable melanoma. The intervention is intended to augment anti-tumor immune responses and improve clinical outcomes when added to standard checkpoint inhibitor therapy.

Also known as: ImmunoBody®

iSCIB1+ in combination with Ipilimumab and Nivolumab

Nivolumab & Ipilimumab DRUG

Nivolumab is a programmed death-1 (PD-1) immune checkpoint inhibitor monoclonal antibody administered according to the protocol-defined treatment regimen. Ipilimumab is a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) immune checkpoint inhibitor monoclonal antibody administered according to the protocol-defined treatment regimen.

Also known as: Yervoy, BMS-734016, Opdivo, BMS-936558

Placebo + Nivolumab and Ipilimumab; iSCIB1+ in combination with Ipilimumab and Nivolumab

Placebo OTHER

The placebo is a Dulbecco's Phosphate-Buffered Saline (D-PBS) solution for intramuscular injection that contains no iSCIB1+ plasmid DNA. It is formulated to be visually and physically indistinguishable from iSCIB1+ and is administered using the same procedures to maintain study blinding. The placebo serves as the comparator in this trial when administered in combination with nivolumab and ipilimumab.

Also known as: Dulbecco's Phosphate-Buffered Saline, D-PBS

Placebo + Nivolumab and Ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant has histologically confirmed, unresectable Stage III or Stage IV melanoma as defined by the AJCC (Gershenwald et al., 2017). Participants with a diagnosis of melanoma of unknown primary are eligible.
• Participant is positive for at least one of the following HLA alleles: HLA- with an HLA type of any one of HLA MHC class I: A2, A3, A31, Bw4, B44 and B35.
• Participant has been clinically evaluated, and checkpoint inhibition has been determined to be an appropriate treatment for their advanced disease.
• Participant's BRAF status must be known; participants with BRAF mutation positive disease may be enrolled without BRAF-inhibitor treatment at the discretion of the Study Investigator.
• Participant has at least one measurable lesion per RECIST 1.1 criteria by computed tomography CT scan or MRI.
• Participant is at least 18 years of age.
• Participant has a life expectancy of more than 6 months.
• Participant has an ECOG performance status of 0 or 1.
• Participant has adequate organ function as determined by the following laboratory values:
• Absolute neutrophil count ≥ 1.5 x 109/L Lymphocyte count ≥0.5 x 109/L Platelet count ≥100 x 109/L Hemoglobin \>9 g/dL (\> 5.6 mmol/L) Serum creatinine or creatinine clearance ≤1.5x ULN \>50 mL/min Serum total bilirubin ≤1.5 x ULN or \<3.0 mg/dL if participant has Gilbert's syndrome Serum transaminases, AST and ALT ≤2.5 x ULN or ≤5.0 x ULN if liver metastases present
• Participant must be able and willing to provide written IRB/REC-approved informed consent prior to any study-related procedure.
• Women of childbearing potential must agree to use highly effective contraceptive methods prior to study entry, for the whole duration of study treatment, and for at least 5 months following the last dose or in accordance with the SmPC of the IC SOC CPI (whichever is most conservative).
• See Appendix D: Guidance on Acceptable Contraceptive Methods for full guidance..
• Women of childbearing potential must have a negative serum pregnancy test at screening and within two days before IMP (or placebo) administration.
• Participant must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

You may not qualify if:

• Participant has a diagnosis of mucosal, ocular or acral melanoma.
• Participant has received prior systemic anti-PD1 treatment for advanced disease.
• Participant has received prior adjuvant treatment, defined as treatment following resection of all detectable disease, within 6 weeks of Day 1 (first dose of IMP).
• Participant has BRAF mutation positive disease with evidence of rapid PD.
• Participant has symptomatic brain metastases or carcinomatous meningitis. Symptomatic brain metastases are defined as brain metastases causing neurological signs or symptoms attributable to intracranial disease and/or requiring corticosteroid therapy for the management of brain metastasis-related symptoms. Participant is expected to require and elect any other form of systemic or localized anticancer therapy while receiving study treatment.
• Participants receive treatment with any investigational product within 28 days (or five half-lives of the treatment concerned if longer than 28 days) prior to Day 1.
• Participant has had a previous or current malignancy within 5 years, with the exception of melanoma and curatively treated local tumors.
• Participant has a concurrent illness/diagnosis which are uncontrolled and/or would preclude study conduct and assessment.
• Participant has NYHA class III or IV heart disease.
• Participant has a history of severe hypersensitivity reaction to treatment with a mAb.
• Participant has an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents above physiological dosing.
• Received a live vaccine or non-live vaccine (including COVID-19 vaccines) within 7 days prior to first dose of study treatment.
• Participant has received systemic steroids or is receiving any other form of immune suppressant medication above physiological dosing within 7 days of Day 1.
• Participant is positive for HIV-1/2 infection or is positive for HBsAg or HCV antigen consistent with active infection.
• Participant has a known current or recent history (within the last year) of substance abuse including illicit drugs or alcohol to the extent where it would negatively affect compliance with the trial protocol based on Study Investigator's decision.

Sponsors & Collaborators

• Scancell Ltd: lead
• PPD, Part of Thermo Fisher Scientific: collaborator
• Egeen: collaborator

Study Sites (2)

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Mount Vernon Cancer Centre

London, United Kingdom

Location

MeSH Terms

Conditions

Melanoma; Skin Neoplasms

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Joe Thornton

CONTACT

44 (0) 1865 582 066; joethornton@scancell.co.uk

Olivia Howard

CONTACT

44 (0) 1865 582 066; oliviahoward@scancell.co.uk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Masking Description If there are other parties who are masked in the clinical trial besides those listed above, use this space to describe those parties.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study uses a randomized, double-blind, placebo-controlled, parallel-group design. Eligible participants will be assigned in a 1:1 ratio to receive either iSCIB1+ plus nivolumab and ipilimumab or placebo plus nivolumab and ipilimumab. Randomization will be stratified according to protocol-defined factors to ensure balanced treatment groups. The study is designed to evaluate whether the addition of iSCIB1+ to standard first-line immunotherapy improves clinical outcomes in participants with advanced unresectable melanoma. Both participants and study personnel involved in study conduct and assessment will remain blinded to treatment assignment throughout the study, except where unblinding is required for participant safety or other protocol-defined reasons. All participants will receive standard-of-care nivolumab and ipilimumab induction treatment followed by nivolumab maintenance therapy in accordance with the protocol. Efficacy, safety, patient-reported outcomes, survival, and bio

Study Record Dates

• First Submitted: September 3, 2026
• First Posted: September 11, 2026
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2032
• Last Updated: September 11, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); GB (1)