Abstract LB214: A DNA plasmid melanoma cancer vaccine, SCIB1, combined with nivolumab + ipilimumab in patients with advanced unresectable melanoma: Efficacy and safety results from the open-label Phase 2 SCOPE Trial
Authors: Heather Shaw, Poulam Patel, Miranda Payne, Satish Kumar, Sarah Danson, Martin Highley, Clare Barlow, Prasad Kellati, Ioannis Karydis, Maria Marples, Kate Young, Pippa Corrie, Robert Miller, Georgia Goodhew, Samantha Paston, Gaelle Cane, Joseph Chadwick, Sabaria Shah, Lindy G. Durrant, Nermeen Varawalla
Journal: Cancer Research (2025)

Abstract Background: Targeting melanoma with T cells drives anti-tumor responses. We previously showed that a DNA vaccine, SCIB1, incorporating T cell epitopes from TRP-2/gp100 into an antibody framework to allow Fc targeting of activated dendritic cells, was successfully as a monotherapy in Stage 3/4 melanoma patients in a Phase 1/2 clinical study. Unresectable melanoma patients showed a 60% ORR and 88% of patients treated with SCIB1, post tumor resection, remained disease free for 5 years [1]. The current SCOPE trial tests the hypothesis that unresectable patients may have an improved response when SCIB1 is combined with checkpoint inhibitors (CPI) compared to CPI alone. Methods: Patients are treated with nivolumab with ipilimumab and SCIB1 (8mg) i.m. using needle-free injection at a fixed dosing schedule for up to 10 doses over 24 months. The CPI therapy is administered i.v. in accordance with their respective SmPC. ORR as measured by RECIST 1.1 in the overall intention-to-treat population is the primary endpoint. The study is designed using Simon's two stage methodology with 80% power when the true response rate is 70% versus 50% RR of no interest with an overall type I error of 5%. In the first stage, 15 patients needed to be enrolled and if there are eight or fewer clinical responses (RECIST 1.1 objective response [CR or PR] within 25 weeks of the first dose of SCIB1), further recruitment would have been stopped. The null hypothesis will be rejected if 27 or more responses are observed in 43 patients. T cell responses are assessed using a cultured ELISpot assay following TRP-2 or gp100 peptides stimulation Results: To date, 43 patients received the combination of SCIB1 with nivolumab and ipilimumab. 25 patients had reached 25 weeks, and had 80% PFS, 84% DCR and 72% ORR with 20% of patients showing a complete response. 94% (16/17) of the clinical responders had a T cell response, 80% (4/5) of the patients with stable disease had a T cell response, 33% (1/3) of patients with progressive disease had a T cell response. T cell receptors isolated from patients showed strong, peptide, ImmunoBody® and tumor recognition. Of interest was that in a patient who showed a pre-vaccinated response to the encoded epitope a different TCR was stimulated by the vaccine. Most of the SCIB1-related adverse events were Grade 1/2. The only Grade 3 related events were a rash, pulmonary embolism, neutropenia and raised GGT. No exacerbation of immune-mediated adverse events was observed when SCIB1 was added to nivolumab with ipilimumab . Conclusions: SCIB1 in combination with nivolumab and ipilimumab as first line treatment for unresectable Stage 3/4 melanoma resulted in 80% 6-month PFS with strong vaccine specific T cell responses without an increase in clinically meaningful adverse events. These results, if confirmed, in a larger patient cohort provide confidence in initiating a randomized registration program in unresectable melanoma patients with our novel DNA plasmid technology. Citation Format: Heather Shaw, Poulam Patel, Miranda Payne, Satish Kumar, Sarah Danson, Martin Highley, Clare Barlow, Prasad Kellati, Ioannis Karydis, Maria Marples, Kate Young, Pippa Corrie, Robert Miller, Georgia Goodhew, Samantha Paston, Gaelle Cane, Joseph Chadwick, Sabaria Shah, Lindy G. Durrant, Nermeen Varawalla. A DNA plasmid melanoma cancer vaccine, SCIB1, combined with nivolumab + ipilimumab in patients with advanced unresectable melanoma: Efficacy and safety results from the open-label Phase 2 SCOPE Trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB214.