IO Biotech’s cancer vaccine Cylembio narrowly misses Phase III primary endpoint in advanced melanoma, but company eyes FDA filing in 2025
IO Biotech reported topline Phase 3 results showing a clinical improvement in PFS for Cylembio plus Keytruda versus Keytruda alone, but the primary endpoint narrowly missed statistical significance.1
In the 407-patient IOB-013/KN-D18 trial, the combination yielded a median PFS of 19.4 months versus 11 months with Keytruda alone, but the result was not statistically significant (HR 0.77; p=0.056). 24
IO Biotech plans to pursue a U.S. FDA biologics license application for Cylembio in advanced melanoma by the end of 2025 despite the Phase 3 miss. 2
A post-hoc analysis in patients without prior anti–PD-1 treatment showed a nominally significant PFS benefit (nominal p=0.037), though OS data remain immature with a favorable trend reported across subgroups. 4
Following the announcement, IO Biotech’s shares fell by about 27% on Aug. 11, 2025, during trading after the investor call. 2
The company characterized the outcome as a “narrow” miss and highlighted consistent PFS improvement and a trend in OS as it engages FDA on a potential path to approval. 15
Trial details:
first-line unresectable or metastatic melanoma; comparison of Cylembio (imsapepimut and etimupepimut, adjuvanted) plus pembrolizumab vs pembrolizumab alone. 123
Sources:
1. https://investors.iobiotech.com/news-events/news/news-details/2025/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/default.aspx
2. https://www.clinicaltrialsarena.com/news/io-biotech-phase-iii-miss-cancer-vaccine-approval/
3. https://www.globenewswire.com/news-release/2025/08/10/3130545/0/en/io-biotech-to-announce-topline-results-of-pivotal-phase-3-trial-of-cylembio-in-combination-with-keytruda-pembrolizumab-as-a-first-line-treatment-for-patients-with-advanced-melanoma.html
4. https://www.fiercebiotech.com/biotech/cancer-vaccines-narrow-phase-3-fail-wont-stop-io-heading-fda
5. https://www.biopharmadive.com/news/IO-biotech-melanoma-cancer-vaccine-study-results-cylembio/757294/