DENVER, Colo., Aug 11, 2025 (247marketnews.com)- IO Biotech (NASDAQ:IOBT) reported topline results from its pivotal Phase 3 trial evaluating Cylembio (imsapepimut and etimupepimut, adjuvanted) in combination with KEYTRUDA (pembrolizumab) as a first-line treatment for patients with unresectable or metastatic melanoma, which demonstrated a clinically meaningful improvement in progression-free survival (PFS), it narrowly missed the pre-specified threshold for statistical significance.
Patients treated with the combination of Cylembio plus pembrolizumab achieved a median PFS of 19.4 months compared to 11.0 months with pembrolizumab alone, representing a hazard ratio (HR) of 0.77 [95% CI: 0.58–1.00]; p=0.056, just above the significance threshold of p ≤ 0.045.
Mai-Britt Zocca, PhD, IO Biotech’s president and CEO, stated, In this study, we observed a highly encouraging improvement in progression free survival and consistent trend in overall survival in patients treated with Cylembio. The magnitude and durability of clinical effect observed consistently across subgroups supports our confidence in Cylembio and its potential as a treatment for advanced melanoma patients. We look forward to engaging with the FDA to determine a potential path to approval based on these data.”
Consistent Efficacy Across Subgroups, Including PD-L1 Negative Patients
The benefit of the combination therapy was evident across nearly all patient subgroups, including those with poor prognostic factors. In patients with PD-L1 negative tumors, a subgroup typically less responsive to immunotherapy, the results were particularly striking:
HR: 0.54 [CI: 0.35–0.85]; nominal p=0.006, with median PFS of 16.6 months vs. 3.0 months for pembrolizumab alone.
In patients without prior neo-adjuvant/adjuvant anti-PD-1 therapy (n=371), the combination also showed a favorable outcome: HR: 0.74 [CI: 0.56–0.98]; nominal p=0.037, with median PFS of 24.8 months vs. 11.0 months in the control arm.
Omid Hamid, MD, Director of Clinical Research and Immunotherapy at The Angeles Clinic and Research Institute, commented, “In this study, patients treated with Cylembio in combination with pembrolizumab have achieved the longest median PFS ever observed in a Phase 3 clinical study in advanced melanoma. The significant benefit seen across patients with poor prognostic factors, including PD-L1 negative patients, cannot be overlooked.”
Safety Profile and Regulatory Path Forward
The combination was well tolerated, with no new safety signals reported. The most common adverse events were injection site reactions, which were generally mild and resolved during treatment.
Inge Marie Svane, MD, PhD, Director of the National Center for Cancer Immune Therapy in Denmark, added, “Since reporting the positive outcome of our Phase 1/2 study (MM1636) in a similar patient population, we have been eagerly awaiting these results supporting the activity of Cylembio combined with an anti-PD-1. These data provide evidence that a therapeutic cancer vaccine can improve progression free survival in patients with metastatic disease.”
Though overall survival (OS) data is still immature, an early trend favoring the combination arm was observed: HR: 0.79 [CI: 0.57–1.10].
Next Steps
IO Biotech plans to meet with the FDA this fall to discuss the totality of data and explore a path toward submission of a Biologics License Application (BLA) for advanced melanoma. More detailed data from the IOB-013 study is expected to be presented at an upcoming medical conference.
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