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Abstract
Background Targeting of melanoma by T cells drives anti-tumour responses. We have previously shown 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 tumour resection, remained disease free for 5 years.1 The 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 and ipilimumab and were also administered with SCIB1 (8mg) i.m. using needle-free injections 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 16 patients received the combination of SCIB1 with nivolumab and ipilimumab. At study entry, all patients were stage IV. 10 patients had reached the first imaging timepoint at 13 weeks, and the objective response rate is 80%. Patients showed a 31–95% reduction in tumour volume between 13 and 25 weeks (figure 1). 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 80% without an increase in clinically meaningful adverse events. These results if confirmed in a larger patient cohort provide confidence in initiating a randomised registration programme in unresectable melanoma patients with our novel DNA plasmid technology.
Acknowledgements We thank all patients for dedicating their time, Ms Georgia Goodhew for providing oversight of the study and members of the investigational teams across the UK for their unwavering support.
Trial Registration https://classic.clinicaltrials.gov/ct2/show/NCT04079166
Reference
Patel PM, et al. A phase I/II trial of SCIB1. Oncoimmunology 2018;22;7(6):e1433516.
Ethics Approval This clinical trial was approved by the North East - York Research Ethics Committee, reference number: 18/NE/0364 . All patients provided informed consent prior to participating in the clinical trial.
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