Scancell's iSCIB1+ Shows 74% Progression-Free Survival at 16 Months in Advanced Melanoma Phase 2 Trial
核心洞察
Scancell's iSCIB1+ (搜索) immunotherapy combined with checkpoint inhibitors achieved 74% progression-free survival at 16 months compared to 50% with standard care alone at 11.5 months in advanced melanoma (搜索) patients.
The therapy demonstrated consistent efficacy across challenging patient subgroups including PD-L1 (搜索) low, BRAF (搜索) wildtype, and those with prior checkpoint inhibitor exposure.
Early overall survival data shows a 14% improvement at 26 months over standard of care, with the company planning Phase 3 registrational trials following positive FDA discussions.
Scancell Holdings (搜索) has reported promising updated Phase 2 data for its DNA immunotherapy iSCIB1+ (搜索) in combination with checkpoint inhibitors for first-line advanced melanoma (搜索) treatment. The SCOPE trial results show progression-free survival (PFS) of 74% at 16 months in the target patient population, substantially outperforming the standard of care combination of ipilimumab and nivolumab alone, which achieved 50% PFS at 11.5 months.
Strong Efficacy Across Patient Subgroups
The updated data from Cohort 3 of the SCOPE trial demonstrates consistent efficacy across key patient subgroups that typically have worse outcomes. The favorable PFS was maintained in patients with PD-L1 (搜索) low expression, BRAF (搜索) wildtype tumors, and those with prior checkpoint inhibitor exposure. Cohort 3 comprised 50 patients total, with 39 in the target HLA (搜索) population, 10 outside the target population, and one non-evaluable due to active brain metastases.
Dr. Heather Shaw, lead for the Medical Oncology Skin Cancer Service at University College London Hospital and principal investigator of the SCOPE trial, stated: "The prolonged progression free survival demonstrates iSCIB1+ (搜索) in combination with checkpoint inhibitors has potential to redefine standard of care. This therapy combination increases the number of advanced melanoma (搜索) patients who would benefit and improves the duration of their clinical response versus equivalent timepoints with checkpoint inhibition alone, thus representing an important step forward for patient outcomes."
Biomarker-Driven Patient Selection
The trial results have enabled Scancell to define a target patient population based on specific human leukocyte antigen (HLA (搜索)) alleles. The therapy is effective in patients with HLA alleles A2, A3, A31, Bw4, B35, and B44, representing 80% of melanoma (搜索) patients. Data from the non-target HLA population showed significantly lower efficacy, with PFS of 20% at 14 months and overall response rate of 20%, supporting the use of HLA typing as a biomarker for patient selection.
In the target population, the overall response rate was 56% with a disease control rate of 79%. The therapy generated iSCIB1+ (搜索) specific T-cell responses that correlated positively with clinical benefit, observed in 72% of patients mounting a T-cell response to both GP100 (搜索) and TRP2 (搜索) epitopes, thereby overcoming immune escape mechanisms.
Regulatory Pathway and Development Plans
Early overall survival data, representing the most advanced data for the SCIB1 platform, shows a 14% improvement at 26 months over standard of care. Dr. Nermeen Varawalla, Chief Medical Officer of Scancell, noted: "iSCIB1+ (搜索), in combination with checkpoint inhibitors, is showing a significant 24% improvement in PFS over standard of care and more efficacy than the first generation SCIB1. This provides additional confidence in the Immunobody® being taken forward towards registrational trials."
The company has received positive feedback from the U.S. Food and Drug Administration and other regulatory agencies supporting plans for Phase 3 registrational development. The discussions have aligned on trial design, dose, manufacturing, and progression-free survival as the expected registrational endpoint.
Treatment Administration and Mechanism
iSCIB1+ (搜索) is administered needle-free intramuscularly and incorporates specific epitopes from the proteins gp100 (搜索) and TRP-2, which play key roles in melanin production. These epitopes were identified from T cells of patients who achieved spontaneous recovery from melanoma (搜索). The positive results with intramuscular administration led the company to discontinue development of intradermal delivery in Cohort 4.
Dr. Phil L'Huillier, CEO of Scancell, commented: "These results give further momentum to our advanced planning for late-stage clinical development. We are continuing our positive discussions with the US FDA and other regulators, with feedback supporting our plans to move iSCIB1+ (搜索) to late-stage development in 2026."
The SCOPE trial is a Phase 2, UK multi-centre open-label study investigating SCIB1/iSCIB1+ (搜索) in combination with checkpoint inhibitors in late-stage melanoma (搜索), enrolling more than 140 patients across four cohorts. The study aims to evaluate efficacy, safety, and durability of the DNA Immunobody® therapies in stage IIIB/IV unresectable metastatic melanoma and define parameters for Phase 3 trial design.