Scancell Holdings (SCLP) Study update summary

Study design and objectives

• Phase II open-label, multi-cohort SCOPE study evaluated off-the-shelf DNA immunotherapies (SCIB1 and iSCIB1+) in advanced melanoma as first-line treatment combined with checkpoint inhibitors at 16 UK sites, enrolling over 140 patients.

• Four cohorts tested first and second generation vaccines with different checkpoint regimens, dosing schedules, and HLA haplotype targeting to select the optimal product and population for phase III.

• iSCIB1+ was designed for broader HLA coverage (80% of patients) and increased potency compared to SCIB1.

• Patient selection biomarker identified for use in registrational studies; HLA typing is standard and widely available.

• Excluded acral melanoma and active brain metastases; required patients to reach week 13 imaging.

Efficacy and clinical outcomes

• Combined cohorts using iSCIB1+ and SCIB1 with ipilimumab/nivolumab showed an ORR of 68.6%, DCR of 88%, and PFS at 22 months of 69%, representing a 20% improvement over standard of care.

• Cohort 3 (iSCIB1+) alone showed ORR of 68.9%, DCR of 86.2%, and PFS of 80.8% at 11 months.

• Cohort 1 (SCIB1 + nivolumab & ipilimumab): ORR 68.4%, DCR 89.5%, PFS at 22 months 64.6%.

• Disease control rate reached 88% and complete response rate was 17.9% among evaluable patients.

• Durable responses observed, with efficacy curves diverging from standard of care over time.

Immunological findings and biomarker development

• T cell responses, especially CD8, correlated with clinical benefit and are predicted by HLA class I alleles (A2, A3, A31, A33, B35, B44), covering 80% of the global melanoma population.

• 61% of cohort 3 patients made a T cell response; 54% of cohort 1 and 72% of cohort 3 responded to both TRP-2 and gp100 epitopes.

• All six epitopes in iSCIB1+ generated targeted T cell responses, with CD8 T cell responses linked to an 83% clinical response rate.

• SCIB1-reactive TCRs showed strong cytotoxic signatures in functional assays.