FDA Grants Fast Track Designation to iSCIB1+ for Advanced Melanoma

The FDA has granted fast track designation (FTD) to iSCIB1+, a DNA plasmid vaccine, for the treatment of advanced melanoma, according to a news release from Scancell Holdings.¹

The designation is supported by maturing efficacy data from the ongoing phase 2 SCOPE trial (NCT04079166), in which iSCIB1+ added to ipilimumab (Yervoy) and nivolumab (Opdivo) resulted in a 69% overall response rate (ORR) and 77% progression-free survival (PFS) at 20 months in a target human leukocyte antigen (HLA)-selected population representing approximately 80% of patients with melanoma.

“This designation is a major achievement for Scancell and important recognition not only of the potential of iSCIB1+, but also of the significant need for new and improved treatment options for patients with advanced melanoma,” said Phil L’Huillier, PhD, MBA, CEO of Scancell, stated in the news release.

Fast Track Designation and Its Implications

The FTD is granted to investigational therapies that address serious conditions and demonstrate potential advantages over available treatments. The designation provides frequent FDA engagement to align on development plans and supports a more efficient path through clinical development. The FTD also confers eligibility for accelerated approval, priority review, and rolling review.

This designation comes after the FDA cleared the investigational new drug application for a global phase 3 trial of iSCIB1+ expected to be initiated in the second half of 2026.² Additional PFS data and early overall survival (OS) data from the SCOPE study are anticipated in the first half of 2027.

SCOPE Phase 2 Trial: Efficacy Data

The open-label multicenter SCOPE trial enrolled over 140 patients with unresectable stage IIIB/IV melanoma in 4 cohorts to receive SCIB1 or iSCIB1+, 2 DNA therapies developed with the Immunobody platform. iSCIB1+ includes additional melanoma-specific epitopes compared with SCIB1.

Across the combined evaluable patients in cohorts 1 and 3, both receiving SCIB1 or iSCIB1+ in combination with ipilimumab and nivolumab, the ORR was 68.6% (46 of 67 patients), with a disease control rate of 88.0% and a complete response rate of 17.9% (12 of 67 patients). These figures compare favorably with the historical 50% ORR reported for ipilimumab plus nivolumab in the pivotal CheckMate 067 trial (NCT01844505) and the approximately 48% ORR observed in the real-world setting.³

PFS results were similarly encouraging. Cohort 1, which evaluated SCIB1 plus ipilimumab and nivolumab, achieved a 12-month PFS of 64.6%. Cohort 3, which evaluated iSCIB1+ with the same backbone, demonstrated an 11-month PFS rate of 80.8% and 20-month PFS rate of 77% in the HLA-selected target population.^1-3 By comparison, ipilimumab plus nivolumab achieved a 12-month PFS of 43.9% in CheckMate 067. Cohort 2, evaluating SCIB1 in combination with pembrolizumab (Keytruda), showed comparable results in 9 target patients before the cohort was stopped due to a change in standard of care in the United Kingdom.

The favorable PFS signal remained consistent across key subgroups that might be expected to have worse outcomes, including patients with PD-L1–low tumors, BRAF wild-type disease, and prior checkpoint inhibitor exposure.

Immunologic Correlates and Biomarker Potential

Translational data from SCOPE provide mechanistic insight into the efficacy results. All 6 epitopes encoded in iSCIB1+ generated targeted T-cell responses. CD8+ T-cell responses were associated with an improved clinical response rate of 83%, and these cytotoxic T cells were shown to both kill tumor cells and induce memory T cells, consistent with the deep and prolonged responses observed clinically.²

Notably, CD8+ T-cell responses could be predicted using human leukocyte antigen (HLA) class I alleles, offering a potential patient selection biomarker for future registrational studies. This HLA-based stratification identifies the target population in which iSCIB1+ is efficacious, approximately 80% of melanoma patients, compared with approximately 40% for the earlier SCIB1 construct, underpinning the decision to advance iSCIB1+ as the candidate of choice for phase 3 development.

Safety Profile

The safety profiles of SCIB1 and iSCIB1+ in combination with checkpoint inhibitors were consistent with those previously reported for ipilimumab and nivolumab alone, with no meaningful increase in treatment-related toxicity attributable to the ImmunoBody therapy. iSCIB1+ is administered via PharmaJet needle-free injection devices for up to 11 doses.

Mechanism, Platform, and Development Context

The DNA ImmunoBody platform uses the body's immune system to identify and destroy tumors by encoding multiple tumor-specific epitopes. The next-generation iSCIB1+ construct incorporates additional melanoma epitopes targeting HLA class I alleles present in 80% of the population, and was developed using the AvidiMab platform to enhance binding avidity and potency relative to the first-generation SCIB1. The therapy demonstrated equipotency and equivalent safety compared with SCIB1 while extending potential benefit to a significantly broader patient population.¹

The FDA clearance of the phase 3 trial of iSCIB1+ will enable further investigation of this therapy. The agreed surrogate end point is PFS, and the trial is designed to enrich enrollment for HLA-selected patients who represent the strongest responders in SCOPE. Scancell previously stated that it was also assessing the potential of a second trial in earlier-stage resectable disease in neoadjuvant and adjuvant settings.³

Advanced melanoma remains a disease of substantial unmet need despite the transformative impact of checkpoint inhibition. Combination checkpoint inhibition such as ipilimumab plus nivolumab is the preferred treatment option patients with metastatic melanoma,⁴ positioning iSCIB1+ as a potential add-on therapy with wide clinical reach if phase 3 results confirm the current findings.

REFERENCES

1. Scancell receives FDA fast track designation for iSCIB1+ in advanced melanoma and provides data update from its SCOPE phase 2 study. News release. Scancell. April 28, 2026. Accessed April 28, 2026. https://tinyurl.com/4u4e43pd

2. Scancell announces FDA clearance of IND application for global phase 3 trial of iSCIB1+ in advanced melanoma. News release. Scancell. January 26, 2026. Accessed April 28, 2026. https://tinyurl.com/54uysjuj

3. Scancell reports phase 2 data showing strongly improved outcomes in late-stage melanoma with its Immunobody iSCIB1+. News release. Scancell. July 22, 2025. Accessed April 28, 2026. https://tinyurl.com/2u4tjb4u

4. NCCN. Clinical Practice Guidelines in Oncology. Melanoma: cutaneous, version 2.2026. Accessed April 28, 2026. https://tinyurl.com/5b39f96p