Topline data from a pivotal phase 3 trial investigating the cancer vaccine Cylembio (imsapepimut and etimupepimut, adjuvanted) plus Keytruda (pembrolizumab) compared with Keytruda alone in patients with unresectable or metastatic (advanced) melanoma were shared in a news release from IO Biotech.
Although Cylembio (an investigational, immune-modulatory, off-the-shelf therapeutic) and Keytruda (an anti-PD-1 therapy) demonstrated clinical improvement in progression-free survival, the combination, evaluated across 407 patients, narrowly missed statistical significance for the primary end point.
“In this study, we observed a highly encouraging improvement in progression-free survival and consistent trend in overall survival in patients treated with Cylembio,” Dr. Mai-Britt Zocca, PhD, president and chief executive officer of IO Biotech, said “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.”
IO Biotech plans to meet with the U.S. Food and Drug Administration (FDA) this fall, based on the phase 3 trial results, as well as present more detailed results from the IOB-013 study at an upcoming medical meeting. Notably, the meeting with the FDA will focus on determining next steps for submission of a Biologics License Application for the treatment of advanced melanoma
Therapeutic Cancer Vaccine Approach Shows Benefit in Advanced Melanoma With Encouraging Survival Trends
Updated findings from the phase 3 study evaluating Cylembio in combination with Keytruda were shared on August 11, 2025. Patients receiving the combination therapy achieved an improvement in progression-free survival compared with those treated with Keytruda alone, with a median progression-free survival of 19.4 months versus 11.0 months, respectively.
“In this study, patients treated with Cylembio in combination with Keytruda have achieved the longest median progression-free survival ever observed in a phase 3 clinical study in advanced melanoma, and in the PD-L1 negative population, patients achieved a remarkable 16.6 months of median progression-free survival, compared to 3.0 months in patients treated with Keytruda alone,” Dr. Omid Hamid, said. “The significant benefit seen across patients with poor prognostic factors, including PD-L1 negative patients, cannot be overlooked. Given the notable safety profile and the strong clinical effect observed with Cylembio, as well as the unmet need in advanced melanoma patients, Cylembio, if approved, has the potential to become a new standard of care for patients with advanced melanoma.”
Hamid is the director of Clinical Research and Immunotherapy at The Angeles Clinic and Research Institute, A Cedars Sinai Affiliate.
Notably, in a subgroup of patients without prior therapy (371 patients), Cylembio plus Keytruda achieved an improvement in progression-free survival, with a median progression-free survival of 24.8 months compared with 11.0 months for the control arm. Improvement in progression-free survival was observed across nearly all patient subgroups, including those with poor prognostic factors.
Moreover, patients with PD-L1–negative tumors experienced a pronounced benefit from the combination therapy, with a median progression-free survival of 16.6 months versus 3.0 months for Keytruda alone.
A trend toward improved overall survival was also observed with the combination, although overall survival data are not yet mature. The regimen was well tolerated, with no new safety signals reported.
“These data show the potential of a therapeutic cancer vaccine in patients with metastatic melanoma,” Dr. Jessica Hassel, lead enrolling investigator for the phase 3 trial, added in the news release. “We were thrilled to play such an important part in this study and to have had the ability to offer our patients an investigational therapy that potentially offers improvements in PFS while not adding significant systemic toxicity.”
Hassel is also a professor at the Department of Dermatology and National Center for Tumor Diseases at the University Hospital Heidelberg, Germany.
More Information on the Phase 3 IOB-013/KN-D18 Trial in Advanced Melanoma
The pivotal phase 3 IOB-013/KN-D18 trial is an open-label, randomized study that enrolled 407 patients with previously untreated, unresectable, or metastatic melanoma across more than 100 sites worldwide. Patients received either Cylembio plus Keytruda (203 patients) or Keytruda alone (204 patients), with progression-free survival as the primary end point.
Secondary endpoints include overall and durable response rates, complete response rate, duration of response, time to complete response, disease control rate, safety, and tolerability.
Cylembio is a therapeutic cancer vaccine designed to target and kill both tumor cells and immune-suppressive cells in the tumor microenvironment. IO Biotech is evaluating Cylembio in multiple studies, including:
- This phase 3 investigation in combination with Keytruda versus Keytruda alone in advanced melanoma
- The Phase 2 IOB-022/KN-D38 basket trial as first-line treatment in advanced solid tumors
- The Phase 2 IOB-032/PN-E40 basket trial as neoadjuvant/adjuvant therapy for solid tumors.
In December 2023, enrollment for the phase 3 trial was completed, and topline results are expected to be reported in the third quarter of 2025; enrollment in both ongoing phase 2 studies are now complete.
“These data provide evidence that a therapeutic cancer vaccine can improve progression free survival in patients with metastatic disease,” Dr. Inge Marie Svane, principal investigator of the ohase 3 trial, added.
Svane is a professor and director of the National Center for Cancer Immune Therapy (CCIT) at the Copenhagen University Hospital, Herlev.
Reference
- “IO Biotech Announces Clinical Improvement in Progression Free Survival Demonstrated in Pivotal Phase 3 Trial of Cylembio® plus KEYTRUDA® (Pembrolizumab) for the Treatment of First-line Advanced Melanoma, but Statistical Significance Narrowly Missed,” by IO Biotech. News release. Aug 11, 2025.
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