FDA Clears Phase 3 Trial of iSCIB1+ for Advanced Melanoma

The U.S. Food and Drug Administration (FDA) has cleared an investigational new drug application for a registrational phase 3 clinical trial of iSCIB1+ for patients with advanced melanoma, a step that allows the global study to move forward with a planned start in 2026.

This trial aims to evaluate whether the therapy can improve progression-free survival for patients with cancer, Scancell Holdings plc announced in a news release.

The clearance is based on data from the phase 2 SCOPE trial, which evaluated iSCIB1+ in combination with Opdivo (nivolumab) plus Yervoy (ipilimumab) in patients with previously untreated unresectable stage 3b or 4 melanoma. According to the company, the FDA agreed that progression-free survival will serve as the surrogate endpoint for the phase 3 study.

Main data that support the findings

Results from the phase 2 SCOPE trial showed that iSCIB1+ demonstrated improved progression-free survival compared with real world standard of care and historic controls, according to Scancell. Interim findings showed a 24% improvement in progression-free survival compared with real world standard of care and historic benchmarks.

More detailed updated data were reported from cohort 3 of the SCOPE trial, which included patients with selected human leukocyte antigen alleles. These alleles represent approximately 80% of patients with melanoma, according to the company. In this target population, progression-free survival was 74% at 16 months.

This outcome was compared with progression-free survival reported for Yervoy plus Opdivo alone, which Scancell described as the current standard of care. In that comparison, progression-free survival was reported as 50% at 11.5 months.

The favorable progression-free survival outcomes with iSCIB1+ were reported to be consistent across several key subgroups analyzed in the trial. These included patients with low PD-L1 expression, patients with BRAF wild-type disease and patients with prior checkpoint inhibitor exposure. According to the company, these subgroups might typically be expected to have worse outcomes.

In addition to progression-free survival, Scancell stated that emerging overall survival signals were observed in the phase 2 SCOPE trial, though specific overall survival data were not detailed in the announcement.

“This IND clearance creates a clear pathway for late-stage registrational development of our iSCIB1+ Immunobody,” Dr. Phil L’Hullier, CEO of Scancell, said in the news release. “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. I take this endorsement of our program as a strong measure of the clinical benefit and safety of our very novel product as well as the quality of our manufacturing and preclinical work. We are continuing our dialogue with regulators broadly as we continue to evaluate all financing options, including partnering discussions, for the phase 3 trial.”

Trial details of the phase 2 SCOPE trial

The phase 2 SCOPE trial (ClinicalTrials.gov identifier NCT04079166) was a UK multi-centre, open-label study that enrolled 140 patients with late-stage melanoma across four cohorts. The study evaluated SCIB1 and iSCIB1+ DNA Immunobody therapies in combination with standard of care checkpoint inhibitors in patients with unresectable stage 3b or 4 melanoma.

Patients enrolled in the trial had not received prior treatment for their advanced melanoma. The study was designed to assess the efficacy, safety and durability of SCIB1 and iSCIB1+ when given alongside checkpoint inhibitors, as well as to define key parameters to inform the design of a phase 3 randomized registration trial.

Based on the phase 2 findings, Scancell selected iSCIB1+ for further development. The therapy is administered via needle-free intramuscular delivery. The company also identified a selection marker during data analysis that it plans to use to enrich the phase 3 trial population for patients more likely to respond to treatment.

The upcoming phase 3 trial is intended to be a registrational study in advanced melanoma, with progression-free survival serving as the agreed surrogate endpoint. Scancell stated that FDA clearance of the investigational new drug appiclation creates a pathway toward late-stage development of iSCIB1+.

Safety of iSCIB1+

According to Scancell, data from the phase 2 SCOPE trial supported both the clinical benefit and safety of iSCIB1+. The company stated that the therapy demonstrated a favorable safety profile in combination with Opdivo and Yervoy, although specific rates or types of side effects were not detailed in the announcement.

Scancell also noted that the FDA’s clearance of the application reflects confidence not only in the clinical data but also in the company’s manufacturing and preclinical work supporting the program. The phase 3 trial is expected to continue evaluating safety alongside efficacy as part of its registrational objectives.

Reference

1. “Scancell announces FDA clearance of IND application for global phase 3 trial of iSCIB1+ in advanced melanoma.” News Release. Scancell Holdings plc.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI and reviewed by a human editor.

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