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Abstract Background Targeting melanoma by 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 evaluated as a monotherapy in a phase 1/2 in stage 3/4 melanoma patients. 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). Methods Patients were treated with nivolumab with ipilimumab and SCIB1 (8mg) i. m. using needle-free injection at a fixed dosing schedule for a total of 10 doses over 24 months. The CPI therapy was administered i. v. in accordance with their respective SmPC. ORR as measured by RECIST 1. 1 in the overall intention-to-treat population was the primary endpoint. The study is designed using Simon's two stage methodology with 80% power when the true response rate is 70% with an overall type I error of 5%. In the first stage, 15 patients will 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 will be stopped. The null hypothesis will be rejected if 27 or more responses are observed in 43 patients. Results 19 patients received the combination of SCIB1 with nivolumab and ipilimumab. At study entry, all patients were stage IV. 13 patients had reached the first imaging timepoint at 13 weeks, and the objective response rate is 85%. 9/9 responses were confirmed in a subsequent scan. Patients showed a 40-95% reduction in tumor volume between 13 and 25 weeks. Most of the SCIB1-related adverse events were Grade 1/2. Only 1 patient reported a Grade 3 rash. No enhancement 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 melanoma improved the ORR to 85% 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 the novel DNA plasmid technology Citation Format: Heather Shaw, Poulam Patel, Miranda Payne, Satish Kumar, Martin Highley, Kellati Prasad, Ruth Board, Clare Barlow, Sarah Danson, Robert Miller, Georgia Goodhew, Fayaz Master, Lindy Durrant. 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 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (7Suppl): Abstract nr CT024.
Shaw et al. (Fri,) studied this question.