Advanced Melanoma |
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Treatment with the ImmunoBody DNA vaccines SCIB1 or iSCIB1+ in combination with standard-of-care (SOC) checkpoint inhibition was effective, safe, and demonstrated durable immune responses in patients with advanced unresectable melanoma, according to data from the ongoing phase 2 SCOPE trial (NCT04079166).1
In cohorts 1 and 3 (n = 67), which evaluated SCIB1 or iSCIB1+, respectively, in combination with ipilimumab (Yervoy) and nivolumab (Opdivo), the combined ORR between the cohorts was 68.6%. This included a complete response (CR) rate of 17.9%. The disease control rate (DCR) was 88.0%. The 12-month progression-free survival (PFS) rate in cohort 1 was 64.6%; in cohort 3, the 11-month PFS rate was 80.8%.
In cohort 2, SCIB1 plus pembrolizumab (Keytruda) demonstrated comparable activity in 9 evaluable patients, although this arm was discontinued due to changes in SOC in the United Kingdom (UK).
These outcomes represent an improvement over historical data in this patient population. In the phase 3 Checkmate 067 study (NCT01844505), the ORR was 50% with SOC ipilimumab plus nivolumab alone, with real-world data showing an ORR of approximately 48%. Moreover, previously reported data showed a 12-month PFS of 43.9% for ipilimumab plus nivolumab, translating to a 20% increase in 12-month PFS with the addition of iSCB1+.
The safety profile of SCIB1/iSCIB1+ plus a checkpoint inhibitor was consistent with previously reported outcomes for ipilimumab plus nivolumab alone, suggesting that the ImmunoBody® platform did not introduce additional toxicity.
“The addition of SCIB1 or iSCIB1+ to SOC checkpoint inhibitors has demonstrated extremely exciting early signals, including improved ORR and PFS to date, without a meaningful increase in treatment-related toxicity,” Dr Heather Shaw, lead of the Medical Oncology Skin Cancer Service at University College London Hospital, London, and the principal investigator of the SCOPE trial, stated in a news release. “These findings highlight the real potential for a significant clinical benefit for patients with advanced melanoma, where there is an unmet need. As the PFS and overall survival [OS] data mature, expediting the planned registrational randomized controlled trial will be critical. This study will have the potential to redefine current treatment paradigms for a disease that remains challenging for many patients.”
ImmunoBody is a customizable DNA vaccine platform designed to express cancer antigen-derived epitopes without affecting the capacity to target activated antigen-presenting cells (APCs) in vivo.2 SCIB1 and its next-generation variant, iSCIB1+, represent Scancell’s lead ImmunoBody candidates. These constructs encode a modified antibody that presents epitopes from gp100 and TRP-2, and they are engineered to target activated APCs.
SCIB1 has demonstrated durable and robust antitumor activity, both as monotherapy and in combination with immune checkpoint inhibitors. iSCIB1+ expands upon this approach by incorporating 6 melanoma-specific epitopes designed to elicit a broader and more potent immune response across a wider patient population.
The phase 2, multicenter, open-label, UK-based SCOPE study evaluated the efficacy, safety, and durability of SCIB1 or iSCIB1+ in combination with checkpoint inhibition in patients with stage IIIB/IV unresectable melanoma.1 The study is designed to enroll more than 140 patients across 4 cohorts.
SCIB1 or iSCIB1+ is being administered by needle-free injection up to 11 times for 85 weeks.3 Treatment with a checkpoint inhibitor started 1 week after the first dose of SCIB1/iSCIB1+ and given as per standard treatment.
The study’s primary end points are ORR, safety, and tolerability. Duration of response, ORR per modified iRECIST 1.1 criteria, PFS, OS, and safety serve as key secondary end points. Exploratory end points include immune response and marker expression.
Additional data from SCOPE showed that all 6 epitopes of iSCIB1+ induced antigen-specific T-cell responses, and CD8-positive T-cell activation was associated with a clinical response rate of 83%.1 These T cells were found to direct tumor cytotoxicity and promote memory T-cell formation, contributing to prolonged clinical benefit. Importantly, the magnitude of CD8-positive T-cell responses was linked to specific HLA class I alleles, indicating a potential role for HLA typing as a biomarker for patient selection.
“iSCIB1+ has shown meaningful benefits in terms of responses, disease control, PFS, and immune responses, which offer a potentially huge improvement for patients,” Nermeen Varawalla, MD, DPhil, MBA, chief medical officer of Scancell, added in the news release. “Furthermore, its strong safety profile suggests that iSCIB1+ could be used in addition to SOC without adding toxicities. These data demonstrate the potential of iSCIB1+ in patients with metastatic melanoma as well as highlight the significant potential in earlier-stage resectable disease when administered in the neoadjuvant/adjuvant setting. The results also provide the option of a biomarker to predict responders, which could be a significant advantage in selecting participants in a future registrational study.”
Scancell asserted that these data provide a potential new benchmark for the treatment of patients with late-stage melanoma in terms of efficacy, durability, immune responses, and safety. Given its broader applicability, improved immunogenicity, and safety profile, iSCIB1+ has been designated as the lead candidate for further clinical development, and plans for a global phase 2b/3 study are underway.
“These data demonstrate that we can add iSCIB1+ to the combination of nivolumab and ipilimumab, or potentially combine it with pembrolizumab, to produce a marked benefit for patients with advanced melanoma,” Phil L’Huillier, PhD, MBA, chief executive officer of Scancell, concluded in the news release. “In the United States alone, ipilimumab plus nivolumab has a market share of 65% to 70% of [patients with] metastatic melanoma. We have selected iSCIB1+ for further development and are now accelerating our planning for a global registrational study in the advanced melanoma setting and assessing the potential of a second trial in earlier lines of disease. We expect to engage with the US FDA on the design of this trial ahead of reporting interim data from cohort 4, which we expect around the [end of 2025].”
References
- Scancell reports Phase 2 data showing strongly improved outcomes in Late-Stage Melanoma with its Immunobody® iSCIB1+. News release. Scancell. July 22, 2025. Accessed July 22, 2025. https://scancell.co.uk/wp-content/uploads/2025/07/20250722-SCOPE-Data_Press-Release-PL.pdf
- Immunobody. Scancell. Accessed July 22, 2025. https://scancell.co.uk/immunobody/
- SCIB1 and iSCIB1+ in melanoma patients receiving nivolumab with ipilimumab or SCIB1 with pembrolizumab (The SCOPE Study). Clinicaltrials.gov. Updated April 4, 2025. Accessed July 22, 2025. https://clinicaltrials.gov/study/NCT04079166