IO Biotech has announced that the Independent Data Monitoring Committee (IDMC) has recommended the continuation of its Phase III IOB-013/KN-D18 clinical trial. This trial is evaluating the investigational therapeutic vaccine IO102-IO103 in combination with KEYTRUDA (pembrolizumab) as a first-line treatment for patients with advanced melanoma. The decision follows an interim analysis of safety and efficacy data.
Interim Analysis Details
The per-protocol interim analysis occurred one year after 225 subjects were randomized. While the interim efficacy analysis, set with a high statistical bar (p≤0.005), did not meet the criteria to declare superiority in objective response rate (ORR), the IDMC's review of safety data revealed no new safety signals. The trial is designed to preserve statistical power for the primary endpoint of progression-free survival (PFS).
Trial Design and Enrollment
The open-label, randomized trial compares the combination of IO102-IO103 with pembrolizumab to pembrolizumab alone in patients with previously untreated, unresectable, or metastatic melanoma. The trial has enrolled 407 patients across more than 100 centers in Europe, the US, Australia, Turkey, South Africa, and Israel.
Primary Endpoint and Future Expectations
The primary endpoint of progression-free survival (PFS) is event-driven and is anticipated to be reached in the first half of 2025. The PFS analysis will be conducted when 226 events (disease progression or death) have been reported and independently reviewed. The trial is powered at 89% to detect a 35% reduction in the risk of an event.
Expert Commentary
IO Biotech president and CEO Mai-Britt Zocca stated, "To date, none of the approved immunotherapeutic combinations for the treatment of advanced melanoma demonstrated statistical significance in ORR in large Phase III trials; nevertheless, these trials achieved statistical significance on PFS." She added, "Based on the 25.5 months median PFS we observed in the Phase I/II trial of IO102-IO103 in combination with a PD-1 inhibitor in advanced melanoma, with no added significant systemic toxicity than that typically seen with anti-PD-1 monotherapy, we remain optimistic about meeting the primary endpoint of PFS, projected to occur in the first half of 2025."
Igor Puzanov, MD, MSCI, FACP, Director, Center for Early Phase Clinical Trials, Chief, Division of Melanoma, Department of Medicine and Investigator for the Phase 3 Study at Roswell Park Comprehensive Cancer Center, commented, "The incidence of melanoma is on the rise and new treatments are needed... I am eagerly awaiting the PFS primary endpoint readout of this Phase 3 trial that could further validate this novel cancer vaccine’s ability to help patients with advanced melanoma who are seeking more efficacious, low treatment-induced toxicity therapy options."
