IO Biotech reports expanded Cylembio results

IO Biotech (IOBT) presented detailed results from its global Phase 3 trial of Cylembio, in combination with Merck’s (MRK) anti-PD-1 therapy Keytruda, for the first-line treatment of patients with unresectable or metastatic melanoma. The data, presented as a proffered paper at the Melanoma and other skin tumors session of the 2025 European Society for Medical Oncology Congress in Berlin, expand upon topline results reported in August. Final results from the Phase 2 basket trial evaluating Cylembio in combination with pembrolizumab in the first-line treatment of advanced non-small cell lung cancer and recurrent/metastatic squamous cell carcinoma of head and neck were also presented. In the randomized Phase 3 trial, 407 patients with previously untreated advanced melanoma received either Cylembio plus pembrolizumab or pembrolizumab alone. Median progression-free survival was 19.4 months for the combination and 11 months for pembrolizumab, narrowly missing the primary endpoint prespecified threshold for statistical significance. Across virtually all subgroups, outcomes in progression-free survival consistently favored the combination regimen, including among patients with PD-L1-negative tumors, BRAFV600 mutated tumors and elevated LDH. In addition, a post-hoc analysis, excluding patients previously treated with anti-PD-1 therapy in neoadjuvant or adjuvant settings, showed mPFS of 24.8 months vs 11 months. The combination was well tolerated, with no increase in immune-mediated adverse events or grade greater than or equal to three treatment-related events compared to pembrolizumab alone. Local vaccine-related injection-site reactions, reported in 56% of patients in the exploratory arm, were generally mild and transient, mostly grade 1/2. IDO1- and PD-L1-specific T-cell responses were expanded in the vaccine arm versus the pembrolizumab arm, reinforcing the therapy’s proposed immune-modulatory mechanism. Also presented at ESMO were final data from the Phase 2 basket trial, evaluating Cylembio in combination with pembrolizumab as treatment for patients with NSCLC or SCCHN. Among 49 efficacy-evaluable patients, mPFS was 8.1 months at 21.4 months of follow-up in NSCLC and 7 months at 18 months of follow-up in SCCHN, with durable responses and encouraging 18-month overall survival rates. The combination’s safety profile remained consistent with anti-PD-1 monotherapy, with no new safety signals.