IO Biotech will present primary Phase 3 results for its IDO/PD-L1-targeted cancer vaccine Cylembio (IO102-IO103) in combination with pembrolizumab versus pembrolizumab alone in first-line advanced melanoma as a late-breaking Proffered Paper at ESMO 2025. Final data from a separate Phase 2 basket trial of the same combination in first-line NSCLC and SCCHN, including updated efficacy, safety, median PFS, landmark PFS, and overall survival, plus translational readouts, will appear in a poster.
The Phase 3 study (IOB-013/KN-D18; NCT05155254) enrolled 407 previously untreated, unresectable, or metastatic melanoma patients across more than 100 sites in the U.S., Europe, Australia, Turkey, Israel, and South Africa, completing enrollment in December 2023. The open-label randomized trial uses PFS as the primary endpoint, with ORR, OS, durability metrics, CR rate, DOR, DCR, and safety as secondaries, and includes planned biomarker work in blood and tumor tissue. IO Biotech has said topline results were reported in the third quarter, but the ESMO slot will provide the first full disclosure and peer discussion. Merck supplied pembrolizumab; IO Biotech retains global commercial rights to the vaccine.
Strategically, this is a high-stakes readout testing whether modulation of the tumor microenvironment via vaccination against IDO1- and PD-L1-positive cells can augment PD-1 blockade without the toxicity and complexity seen with some dual-immunotherapy regimens. The field has moved toward combination backbones in melanoma, with LAG-3/PD-1 already reshaping practice. A clean PFS win with tolerable safety would position Cylembio+pembrolizumab as a competitive, operationally straightforward alternative on a widely used PD-1 backbone. Conversely, the shadow of prior IDO failures raises the bar for demonstrating not just statistical significance but clinically meaningful, durable benefit with clear mechanistic support from translational data.
For sites and CROs, the program reflects a pragmatic design: standard imaging-based PFS in an open-label setting, global recruitment with rapid accrual, and an off-the-shelf agent layered onto an established SOC. If positive, adoption at community and academic centers would hinge on manageable visit schedules for vaccine administration and monitoring for incremental immune-related AEs versus PD-1 alone. The biomarker plan matters operationally; if the signal concentrates in defined subsets, sponsors and sites could face added screening steps and lab logistics, but a biomarker-agnostic benefit would simplify rollout. Regulators will look for consistency across geographies and subgroups as well as the magnitude and durability of effect, particularly given increasing scrutiny of add-on combinations that raise cost and complexity.
The Phase 2 basket poster in NSCLC and SCCHN provides a read on portability beyond melanoma. Any convergence between efficacy and translational signatures across indications would strengthen the platform narrative and guide expansion strategy. For vendors, central imaging and translational assays will be focal points; for payers and health systems, total cost of care will depend on whether the regimen averts downstream toxicity or resource use compared with other combo options.
The key watch items at ESMO are the size of the PFS effect versus pembrolizumab monotherapy, early OS trajectory, complete and durable response rates, and the safety delta. Translational evidence linking target engagement to clinical benefit will influence regulatory dialogue and potential labeling. If the data are strong, expect rapid movement toward regulatory interactions and clarity on commercialization partners and manufacturing scale-up; if the benefit is modest or safety adds friction, positioning against entrenched PD-1/LAG-3 combinations becomes challenging. The basket trial results will signal whether IO Biotech is building a melanoma-focused franchise or a broader PD-1-anchored platform.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
