iSCIB1+ in Combination With Ipilimumab and Nivolumab as First-Line Treatment for Advanced Unresectable Melanoma
Trial statusNot yet recruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorScancell Ltd
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
iSCIB1+
Biological/VaccineiSCIB1+ 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.
Nivolumab & Ipilimumab
DrugNivolumab 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.
Placebo
Other interventionThe 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.
Treatment groups
550 Participants
are divided into 2 treatment groupsGroup A: iSCIB1+ in combination with Ipilimumab and NivolumabExperimental treatment 2 interventions
Group B: Placebo + Nivolumab and IpilimumabPlacebo comparator 2 interventions
Trial outcomes
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.
Time frame
Up to 4 years after randomization.Secondary outcomes
1
Overall Survival (OS)
Overall survival, defined as the time from randomization to death from any cause.
Time frame
Up to approximately 4 years months after randomization.2
Objective Response Rate (ORR)
Objective response rate, defined as the proportion of participants achieving a confirmed complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by BICR.
Time frame
Up to 4 years after randomization.3
Duration of Response (DoR)
Duration of response, defined as the time from first documented objective response (CR or PR) until disease progression per RECIST v1.1 or death from any cause.
Time frame
Up to 4 years after randomization.4
Disease Control Rate (DCR)
Disease control rate, defined as the proportion of participants achieving complete response, partial response, or stable disease according to RECIST v1.1 as assessed by BICR.
Time frame
Up to 4 years after randomization.Other outcomes
1
Immune Response to iSCIB1+: Change from baseline in antigen-specific T-cell response measured by IFN-γ ELISpot assay
Antigen-specific cellular immune responses to TRP-2 and gp100 melanoma antigens will be evaluated using IFN-γ ELISpot assays on peripheral blood samples collected from a subset of participants.
Time frame
From informed consent and up to 4 years from randomization2
Change from baseline in exploratory tumor, blood, and immune biomarker levels
Analysis of changes in exploratory tumor, blood, and immune biomarkers measured in tissue and blood samples collected during the study. Biomarker measurements may include gene expression, circulating tumor DNA, immune cell populations, cytokines, and other exploratory markers.
Time frame
From informed consent until completion of study participation (i.e. up to 4 years)3
Change from baseline in exploratory immune-related biomarker measurements
Exploratory assessment of changes in immune-related biomarkers, including PD-1, PD-L1, CTLA-4, CD3+, CD4+, CD8+ cell markers, cytokines, T-cell receptor repertoire, tumor infiltrating lymphocytes, and circulating tumor DNA measured in tumor tissue and blood samples.
Time frame
From baseline and up to 4 years from day 1.Sponsors and contacts
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Source ClinicalTrials.gov
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