IO Biotech's Cancer Vaccine Shows 25.5-Month Median Progression-Free Survival in Five-Year Melanoma Study
Key Insights
IO Biotech published five-year follow-up data from its Phase 1/2 MM1636 trial showing IO102-IO103 combined with nivolumab achieved a median progression-free survival of 25.5 months in metastatic melanoma patients.
The study demonstrated a median duration of response exceeding 53 months and median overall survival of 60 months, with vaccine-specific immune biomarkers suggesting distinct immune modulation not seen with anti-PD-1 (search) monotherapy.
These results supported FDA Breakthrough Therapy Designation and provided the foundation for IO Biotech's Phase 3 trial IOB-013/KN-D18, which completed enrollment with 407 patients in December 2023.
IO Biotech announced the publication of five-year clinical outcomes from its Phase 1/2 MM1636 trial in Nature Communications, demonstrating sustained efficacy of its investigational cancer vaccine IO102-IO103 in combination with PD-1 (search) blockade for first-line metastatic melanoma treatment. The long-term analysis revealed a median progression-free survival of 25.5 months, reinforcing the potential of immune-modulatory vaccination approaches in oncology.
Durable Clinical Activity and Immune Response
The MM1636 trial enrolled 30 patients with metastatic melanoma at Copenhagen University Hospital, Herlev. Patients received IO102-IO103, a peptide vaccine targeting IDO1 (search) and PD-L1 (search) expressing cells, in combination with nivolumab as first-line treatment. The five-year follow-up analysis demonstrated notable clinical durability with a median duration of response exceeding 53 months and an impressive median overall survival of 60 months.
"We are very encouraged that the long-term follow up data confirm the earlier results reported from this study," said Inge Marie Svane, MD, PhD, Professor and Director of the National Center for Cancer Immune Therapy at Copenhagen University Hospital, Herlev, and Principal Investigator in the IOB-013 Phase 3 Trial. "The notable median duration of response of more than 53 months and an impressive median overall survival of 60 months support the potential of IO102-IO103 as a first-line therapy for melanoma as part of a combination regimen."
Vaccine-Specific Immune Biomarkers
The study identified potential vaccine-specific immune biomarkers of long-term benefit that were not observed in a matched anti-PD-1 (search) monotherapy cohort. These findings suggest distinct vaccine-induced immune modulation that increases anti-tumor activity, providing scientific insights into the contributions of IDO1 (search) and PD-L1 (search) vaccination to PD-1 blockade effectiveness.
"These are very exciting data that continue reinforcing the scientific foundation of our immune-modulatory therapeutic approach and strengthens our belief in its potential to transform patient care," said Mads Hald Andersen, DMSc, PhD, Director of the Center for Cancer Immune Therapy and scientific co-founder of IO Biotech. "IDO1 (search) and PD-L1 (search) are immune suppressive targets expressed in many cancers hence, we believe that IO102-IO103 could have pan-tumor activity."
Treatment Protocol and Platform Technology
In the MM1636 trial, patients received nivolumab according to the approved melanoma label at 3mg/kg bi-weekly for up to two years. IO102-IO103 was administered from the start of nivolumab treatment every second week for the first six weeks, then every fourth week for 41 weeks. The trial assessed safety, immune response in blood and biopsies, and efficacy.
IO Biotech's T-win platform represents a novel approach to cancer vaccines designed to activate T cells targeting both tumor cells and immune-suppressive cells in the tumor microenvironment. The company is developing off-the-shelf, immune-modulatory therapeutic cancer vaccines based on this platform technology.
Regulatory Recognition and Phase 3 Development
The MM1636 results supported a Breakthrough Therapy Designation from the FDA for the treatment of unresectable/metastatic melanoma in combination with pembrolizumab. Together with available preclinical and translational data, these findings served as the foundation for IO Biotech's Phase 3 clinical trial IOB-013/KN-D18.
The Phase 3 trial was an open-label, randomized study evaluating Cylembio (search) (IO102-IO103) in combination with Merck (search)'s pembrolizumab versus pembrolizumab alone in patients with previously untreated, unresectable or metastatic melanoma. Enrollment was completed by December 2023 with 407 patients enrolled from more than 100 centers across the United States, Europe, Australia, Turkey, Israel and South Africa. The primary endpoint was progression-free survival, with secondary endpoints including overall response rate, overall survival, and safety parameters.
"There continues to be a significant unmet need for innovative therapies that improve outcomes for cancer patients," said Mai-Britt Zocca, PhD, President and CEO of IO Biotech. "These data strengthen our belief in Cylembio (search) and in our approach to develop off-the-shelf, immune modulatory therapeutics, with pan-cancer potential."