Scancell has reported updated results from its Phase 2 SCOPE trial, showing its next-generation Immunobody therapy, iSCIB1+, produced a 69% response rate in patients with late-stage melanoma who have a target HLA type — significantly outperforming the current standard of care.

The data from cohorts 1 and 3 of the study, which tested SCIB1 and iSCIB1+ in combination with ipilimumab and nivolumab, showed an overall response rate (ORR) of 68.6% across 67 evaluable patients, a disease control rate of 88.0%, and a complete response rate of 17.9%. This compares favourably with ORRs of 48–50% typically observed with ipilimumab and nivolumab alone.

Twelve-month progression-free survival was also notably improved. Cohort 1 achieved 64.6%, and Cohort 3 reached 80.8% at 11 months, compared with a previously reported 12-month PFS of 43.9% for standard combination treatment. No new safety issues were identified, with the addition of iSCIB1+ appearing to be well tolerated.

Scancell has now selected iSCIB1+ as the lead candidate for further development and is accelerating plans for a registrational Phase 2b/3 global trial. The company also highlighted the emergence of a potential biomarker based on CD8 T cell responses linked to HLA class 1 alleles — opening the door to future patient stratification.

Dr Heather Shaw, lead for the medical oncology skin cancer service at University College London Hospital and principal investigator of the SCOPE trial, said:

“The addition of SCIB1 or iSCIB1+ to standard-of-care checkpoint inhibitors has demonstrated extremely exciting early signals, including improved overall response rates and progression-free survival to date, without a meaningful increase in treatment-related toxicity. These findings highlight the real potential for a significant clinical benefit for patients with advanced melanoma, where there is an unmet need.”

The next-generation Immunobody therapy iSCIB1+ includes multiple epitopes designed to target HLA class I alleles in 80% of the population, and incorporates avidity-enhancing features from Scancell’s AvidiMab platform. It showed equipotency and safety comparable to SCIB1, but with the added advantage of broader applicability.

Scancell’s chief medical officer Dr Nermeen Varawalla said:

“iSCIB1+ has shown meaningful benefits in terms of responses, disease control, progression-free survival and immune responses, which offer a potentially huge improvement for patients. Furthermore, its strong safety profile suggests that iSCIB1+ could be used in addition to SoC without adding toxicities.”

Importantly, all six DNA epitopes in the iSCIB1+ construct generated targeted T cell responses. Among patients with CD8 T cell activation, the response rate was 83%, suggesting the potential for a predictive biomarker based on HLA profiling.

Dr Phil L’Huillier, chief executive officer of Scancell, added: “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. In the US alone, ipilimumab plus nivolumab has a market share of 65–70% of metastatic melanoma patients.”

“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 FDA on the design of this trial ahead of reporting interim data from Cohort 4, which we expect around the year end.”

SCOPE is a UK-based Phase 2 open-label study investigating SCIB1/iSCIB1+ in combination with checkpoint inhibitors in over 140 patients with advanced unresectable melanoma. The trial’s goal is to evaluate efficacy, durability, safety, and inform the design of a registrational Phase 2b/3 study.