お知らせ • Oct 21
IO Biotech Presents Phase 3 Results for Cylembio Plus KEYTRUDA (Pembrolizumab) in First-Line Advanced Melanoma at ESMO 2025
IO Biotech presented detailed results from its global Phase 3 trial (IOB-013/KN-D18) of Cylembio (imsapepimut and etimupepimut, adjuvanted), in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab), for the first-line treatment of patients with unresectable or metastatic (advanced) melanoma. Cylembio plus pembrolizumab achieved a clinically relevant 19.4 months median progression free survival (mPFS) compared to 11.0 months mPFS with pembrolizumab alone; study narrowly missed progression free survival (PFS) primary endpoint for statistical significance. Improvement in PFS favored the combination across virtually all subgroups, notably in patients with PD-L1-negative tumors, BRAFV600-mutated tumors, and elevated LDH, without adding any systemic toxicity compared to pembrolizumab alone. 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 11.0 months for pembrolizumab (hazard ratio [HR] 0.77; 95% CI, 0.58–1.00; p=0.0558), narrowly missing the primary endpoint prespecified threshold for statistical significance (p=0.045). Across virtually all subgroups, outcomes in progression-free survival consistently favored the combination regimen, including among patients with PD-L1–negative tumors (16.6 vs 3.0 months; HR 0.54; 95% CI, 0.35-0.85), BRAFV600 mutated tumors (HR 0.60; 95% CI, 0.40-0.90), and elevated LDH (HR 0.60; 95% CI, 0.39-0.92). 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 11.0 months (HR 0.74; 95% CI, 0.56–0.98). The combination was well tolerated, with no increase in immune-mediated adverse events (34.0% vs 38.4%) or grade =3 treatment-related events (14.5% vs 15.6%) 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. Final results from the Phase 2 basket trial (IOB-022/KN-D38) evaluating Cylembio in combination with pembrolizumab in the first-line treatment of advanced non-small cell lung cancer (NSCLC) and recurrent/metastatic squamous cell carcinoma of head and neck (SCCHN) were also presented. Among 49 efficacy-evaluable patients (31 with NSCLC and 18 with SCCHN), mPFS was 8.1 months at 21.4 months of follow-up in NSCLC and 7.0 months at 18 months of follow-up in SCCHN, with durable responses and encouraging 18-month overall survival (OS) rates. The combination’s safety profile remained consistent with anti–PD-1 monotherapy, with no new safety signals. Cylembio (imsapepimut and etimupepimut, adjuvanted) is an investigational, immune-modulatory, off-the-shelf therapeutic cancer vaccine candidate designed to kill both tumor cells and immune-suppressive cells in the tumor microenvironment (TME) by stimulating activation and expansion of T cells against indoleamine 2,3-dioxygenase 1 (IDO1) positive and/or programmed death-ligand 1 (PD-L1) positive cells. The company is currently conducting a pivotal Phase 3 trial (IOB-013/KN-D18; NCT05155254) investigating Cylembio in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) versus pembrolizumab alone in patients with advanced melanoma, a Phase 2 basket trial (IOB-022/KN-D38; NCT05077709) investigating Cylembio in combination with pembrolizumab as first line treatment in patients with advanced solid tumors, and a Phase 2 basket trial (IOB-032/PN-E40; NCT05280314) investigating Cylembio in combination with pembrolizumab as neo-adjuvant/adjuvant treatment of patients with solid tumors. Enrollment in the Phase 3 trial was completed rapidly by December 2023 with topline results from this trial reported in the third quarter of 2025. Enrollment in the two ongoing company-sponsored Phase 2 clinical trials is now complete. The clinical trials are sponsored by IO Biotech and conducted in collaboration with Merck, which is supplying pembrolizumab. IO Biotech maintains global commercial rights to Cylembio. Cylembio is a registered trademark of IO Biotech ApS, a subsidiary of IO Biotech. KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (known as MSD outside of the US and Canada). IOB-013/KN-D18 (ClinicalTrials.gov: NCT05155254) is an open label, randomized Phase 3 pivotal clinical trial evaluating Cylembio in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) versus pembrolizumab alone in patients with previously untreated, unresectable or metastatic (advanced) melanoma. Enrollment in the trial was completed by December 2023 with a total of 407 patients enrolled from more than 100 centers across the United States, Europe, Australia, Turkey, Israel and South Africa. The primary endpoint of the study was progression-free survival. Secondary endpoints include overall response rate, overall survival, durable objective response rate, complete response rate, duration of response, time to complete response, disease control rate, and incidence of adverse events and serious adverse events (safety and tolerability). Biomarkers in the blood and tumor tissue will also be assessed as exploratory endpoints. The company reported topline results from this trial in the third quarter of 2025. IO Biotech is sponsoring the Phase 3 trial and Merck is supplying pembrolizumab. IOB-022/KN-D38 (NCT05077709) is a non-comparative, open label trial to investigate the safety and efficacy of Cylembio in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in the first-line treatment of metastatic non-small cell lung cancer (NSCLC) or recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) at sites in the United States, Spain, and the United Kingdom. IO Biotech is sponsoring the Phase 2 trial and Merck is supplying pembrolizumab.
