Novel Cancer Vaccine Combos Show Efficacy, Safety in Late-Stage Melanoma

The SCIB1/iSCIB1+ cancer vaccines plus nivolumab and ipilimumab improved responses vs nivolumab and ipilimumab alone in patients with melanoma.

SCIB1/iSCIB1+ Immunobody® DNA active immunotherapies in combination with checkpoint inhibitors demonstrated positive efficacy, durability, immune responses, and safety in patients with late-stage melanoma, according to a press release on topline results from the phase 2 SCOPE trial (NCT04079166) from the developer, Scancell Holdings.1

In cohorts 1 and 3, patients received SCIB1 or iSCIB1+, respectively, plus ipilimumab (Yervoy) and nivolumab (Opdivo). For all evaluable patients in cohorts 1 and 3, the combined overall response rate (ORR) was 68.6% (n = 46/67), with a complete response (CR) rate of 17.9% (n = 12/67) and a disease control rate (DCR) of 88.0%.

In cohort 2, patients received SCIB1 plus pembrolizumab (Keytruda), which elicited comparable results in 9 target patients after the cohort was stopped due to a change in the UK’s standard of care.

It was noted in the release that these results achieved a substantial improvement compared with the previously reported ORR of 50% with ipilimumab and nivolumab in the phase 3 CheckMate 067 trial (NCT01844505) and approximately 48% in real-world settings.2

In cohort 1, the 12-month progression-free survival (PFS) rate was 64.6%, and in cohort 3, the 11-month PFS rate was 80.8%.

Results from SCOPE compared favorably with the previously reported 12-month PFS of 43.9% with ipilimumab plus nivolumab.

Further, recently updated data demonstrated that the 6 epitopes in the DNA Immunobody® therapy iSCIB1+ generated targeted T-cell responses; CD8 T-cells correlated with an improved clinical response rate of 83%. The CD8 T-cell response was predictable via the human leukocyte antigen (HLA) class I alleles.

iSCIB1+ has additional epitopes that target HLA class I alleles that are present in 80% of the population, has improved avidity from Scancell’s AvidiMab® platform, and showed equipotency and equal safety compared with SCIB1.

The investigators added that iSCIB1+ affected a wider patient population vs SCIB1, with 80% vs 40%, respectively, and thus will be the candidate of choice for further development.

“The addition of SCIB1 or iSCIB1+ to standard-of-care checkpoint inhibitors has demonstrated extremely exciting early signals, including improved [ORR] and [PFS] to date, without a meaningful increase in treatment-related toxicity,” stated Heather Shaw, FRCP, lead for the Medical Oncology Skin Cancer Service at University College London Hospital, London and principal investigator of the SCOPE trial, in the press release.1 “These findings highlight the real potential for a significant clinical benefit for patients with advanced melanoma, where there is an unmet need.”

SCOPE is an open-label, single-arm trial designed to evaluate 2 new cancer vaccines, SCIB1 and iSCIB1+, in combination with nivolumab and ipilimumab, and to inform the design of a phase 2b/3 randomized trial. SCOPE plans to enroll more than 140 patients across 4 cohorts.

Study treatment consisted of up to 11 doses of either SCIB1 or SCIB1+ for up to 85 weeks in combination with nivolumab with ipilimumab or SCIB1 with pembrolizumab.

Eligible patients were 18 years or older with a histologically confirmed diagnosis of unresectable stage III or IV melanoma and no receipt of prior systemic treatment for advanced disease, although prior adjuvant or neoadjuvant therapy was permitted.3 Additional eligibility criteria included a known BRAF status, HLA-A2-positivity, at least 1 measurable lesion per RECIST v1.1 guidelines, an ECOG performance status of 0 or 1, and at least 3 months of life expectancy.

Those with mucosal, acral, or ocular melanoma; central nervous system metastases or carcinomatous meningitis; a previous or current malignancy with the exception of melanoma; and history of severe hypersensitivity to monoclonal antibody treatment were excluded from the trial.

The trial’s primary end points were safety and tolerability assessed via evaluation of adverse events, safety and tolerability assessed via evaluation of vital signs, and ORR. Secondary end points included duration of response, PFS rate, and overall survival rate; exploratory end points were immune response and marker expression.

Regarding safety, the safety profiles of the SCIB1 and iSCIB1+ combinations with standard of care were consistent with what was previously observed with nivolumab and ipilimumab combinations, suggesting that the cancer vaccines did not add safety issues and were well tolerated.

References

1. Scancell reports phase 2 data showing strongly improved outcomes in late-stage melanoma with its Immunobody® iSCIB1+. News release. Scancell Holdings plc. July 22, 2025. Accessed July 22, 2025. https://tinyurl.com/muvpjpe2
2. Serra-Bellver P, Versluis JM, Oberoi HK, et al. Real-world outcomes with ipilimumab and nivolumab in advanced melanoma: a multicentre retrospective study. Eur J Cancer. 2022;176:121-132. doi:10.1016/j.ejca.2022.09.004
3. 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://tinyurl.com/5n8xrpr4