Scancell Secures FDA Clearance for Pivotal Phase 3 Melanoma Trial as Novel Immunotherapy Shows 24-Point Survival Advantage

In a significant regulatory milestone that could reshape melanoma treatment, UK-based Scancell Holdings announced on January 27, 2026, that the FDA has cleared its Investigational New Drug (IND) application for a registrational Phase 3 trial of iSCIB1+, its novel DNA immunotherapy for advanced melanoma. The clearance follows compelling Phase 2 data showing a remarkable 24-percentage-point improvement in progression-free survival compared to standard care, positioning the therapy as a potential game-changer in one of oncology's most challenging treatment areas.

Breakthrough Results Drive Regulatory Confidence

The FDA's clearance stems from robust data from Scancell's completed 140-patient SCOPE Phase 2 trial, which evaluated iSCIB1+ in combination with checkpoint inhibitors nivolumab and ipilimumab in previously untreated patients with unresectable stage IIIB/IV melanoma. The results demonstrated what can only be described as exceptional efficacy: progression-free survival reached 74% at 16 months in the target population, compared to the 50% at 11.5 months typically seen with current standard-of-care checkpoint inhibitor combinations alone.

Perhaps more importantly, this survival advantage remained consistent across traditionally difficult-to-treat patient subgroups, including those with PD-L1 low expression, BRAF wildtype tumors, and patients with prior checkpoint inhibitor exposure. This broad efficacy profile suggests iSCIB1+ could benefit a wider patient population than initially anticipated, potentially addressing some of the limitations that have constrained current immunotherapy approaches.

Revolutionary DNA Immunotherapy Platform

What sets iSCIB1+ apart from conventional treatments is its innovative mechanism of action. As a DNA Immunobody, the therapy works by training the patient's immune system to recognize and attack specific tumor-associated antigens that are commonly expressed in melanoma cells. Unlike traditional vaccines that rely on external proteins, this DNA-based approach instructs the patient's own cells to produce the target antigens, potentially creating more durable and comprehensive immune responses.

The therapy is administered needle-free intramuscularly, addressing patient compliance concerns while potentially improving immune activation. This delivery method, combined with the therapy's ability to generate both cellular and humoral immune responses, represents a sophisticated evolution in cancer immunotherapy design.

Crucially, Scancell has identified a selection marker that allows enrichment of the Phase 3 trial for likely responders. This biomarker-driven approach targets patients with specific human leukocyte antigen (HLA) alleles, representing approximately 80% of melanoma patients. This precision medicine strategy could maximize the therapy's benefit while minimizing exposure for patients unlikely to respond.

Addressing Critical Unmet Medical Need

The regulatory milestone comes at a time when melanoma treatment, while significantly improved by checkpoint inhibitors, still faces substantial challenges. Despite advances with drugs like nivolumab and ipilimumab, many patients either fail to respond initially or develop resistance over time. The 24-percentage-point improvement in progression-free survival demonstrated by iSCIB1+ represents one of the largest efficacy gains seen in melanoma immunotherapy in recent years.

Dr. Phil L'Huillier, CEO of Scancell, emphasized the significance of the regulatory endorsement: "This IND clearance creates a clear pathway for late-stage registrational development of our iSCIB1+ Immunobody. Data from the Phase 2 SCOPE trial shows a significant improvement in progression free survival as well as emerging overall survival with iSCIB1+ compared to historic benchmarks."

Strategic Positioning and Market Implications

The FDA clearance positions Scancell to compete in the lucrative melanoma therapeutics market, which has been dominated by checkpoint inhibitors and targeted therapies. The company's approach of combining its novel immunotherapy with established checkpoint inhibitors could offer the best of both worlds: the proven efficacy of current standards combined with the enhanced immune activation provided by DNA immunotherapy.

The registrational Phase 3 trial design, with progression-free survival as the agreed surrogate endpoint, suggests a potentially accelerated path to approval if the Phase 2 results are confirmed in the larger study. This regulatory strategy reflects the FDA's recognition of the significant unmet need in melanoma treatment and the compelling nature of the preliminary data.

Looking Ahead

As Scancell prepares to initiate its pivotal Phase 3 trial in 2026, the company continues dialogue with regulators globally while evaluating financing options, including potential partnerships. The strong Phase 2 data, combined with FDA clearance and a clear regulatory pathway, positions iSCIB1+ as one of the most promising melanoma therapies in late-stage development.

For the thousands of patients diagnosed with advanced melanoma each year, iSCIB1+ represents hope for significantly improved outcomes through a novel approach that harnesses the body's own immune system. If the Phase 3 trial confirms the remarkable efficacy signals seen in Phase 2, this DNA immunotherapy could establish a new standard of care in melanoma treatment, demonstrating the continued evolution and promise of precision immunotherapy approaches.