IO Biotech's Cylembio Vaccine Shows Promise in Phase 3 Trial for Advanced Melanoma Treatment

IO Biotech's Cylembio vaccine, in combination with Merck's KEYTRUDA, demonstrated improved progression-free survival in a Phase 3 trial for advanced melanoma patients, but narrowly missed statistical significance. The combination therapy showed a hazard ratio of 0.77 and a median progression-free survival of 19.4 months compared to 11.0 months for KEYTRUDA alone. The treatment was well-tolerated, with injection site reactions being the most common adverse event.

IO Biotech has announced topline results from its pivotal Phase 3 trial of Cylembio, an investigational, immune-modulatory, off-the-shelf therapeutic cancer vaccine, in combination with Merck's anti-PD-1 therapy, KEYTRUDA (pembrolizumab). The trial evaluated Cylembio in combination with KEYTRUDA versus KEYTRUDA alone as a first-line treatment in 407 patients with unresectable or metastatic (advanced) melanoma [1].

The primary endpoint was progression-free survival (PFS) as assessed by a blinded independent review committee per RECIST v1.1. The study demonstrated an improvement in PFS with a hazard ratio of 0.77 (95% CI: 0.58-1.00; p=0.056; threshold for significance p=0.045). Patients treated with Cylembio plus pembrolizumab achieved a median PFS of 19.4 months compared to 11.0 months for those treated with pembrolizumab alone. Although not yet mature, a trend toward an improvement in overall survival was observed [2].

The combination was well-tolerated, with no new safety signals observed. Injection site reactions were the most commonly reported adverse events, with 56% of patients in the combination arm reporting an event [3].

The trial highlighted two key subgroups where Cylembio shone: PD-L1 negative patients and treatment-naïve patients. For PD-L1 negative patients, the median PFS improved from 3.0 months to 16.6 months, with a hazard ratio of 0.54 (CI 0.35-0.85) (nominal p=0.006). Among treatment-naïve patients, the median PFS improved from 11.0 months to 24.8 months, with a hazard ratio of 0.74 (CI 0.56-0.98) (nominal p=0.037) [3].

IO Biotech plans to meet with the FDA in late 2025 to discuss a Biologics License Application (BLA) for Cylembio in PD-L1 negative or treatment-naïve melanoma patients. If the FDA accepts subgroup data as a basis for approval, Cylembio could secure a niche market in a $10 billion+ advanced melanoma space [3].

The trial's durability of PFS curves and consistent subgroup results provide a strong foundation for regulatory engagement. Investors who focus on the broader implications, such as the potential for subgroup-driven approvals and the unmet need in PD-L1 negative melanoma, may find this setback to be a buying opportunity.

References:
[1] https://www.marketscreener.com/news/io-biotech-announces-topline-results-of-pivotal-phase-3-trial-of-cylembio-in-combination-with-keytru-ce7c5ed3de80f722
[2] https://www.marketscreener.com/news/io-biotech-announces-clinical-improvement-in-progression-free-survival-demonstrated-in-pivotal-phase-ce7c5ed2de8ef727
[3] https://www.ainvest.com/news/io-biotech-cylembio-trial-lesson-incremental-progress-long-term-2508/