News|Articles|October 3, 2025
Redirection for Novel Melanoma Vaccine Candidate Following FDA Meeting
Author(s)Andrea Eleazar, MHS
Fact checked by: Sabrina Serani
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Key Takeaways
- The FDA advised against BLA submission for IO Biotech's melanoma vaccine due to narrowly missing statistical significance in the phase 3 trial.
- The IOB-013 study showed a median PFS improvement with the vaccine combination, but the primary endpoint's P-value exceeded the significance threshold.
FDA advises against BLA submission for IO Biotech's melanoma vaccine after phase 3 trial results narrowly missed statistical significance.
During a pre-biologics license application (BLA) meeting between IO Biotech and the US FDA regarding the investigational melanoma vaccine, imsapepimut and etimupepimut (IO102-IO103; Cylembio), the FDA has advised IO Biotech against BLA submission, a recommendation based on
“We had a productive meeting with FDA; while this is not the outcome we had hoped for, we respect FDA’s feedback and remain confident in the therapeutic potential of [imsapepimut and etimupepimut],” said Mai-Britt Zocca, PhD, president and chief executive officer of IO Biotech, in a press release.1
What Is the IOB-013 Study Investigating?
The phase 3 IOB-013 study is a multicenter, open-label, randomized study evaluating the combination of imsapepimut and etimupepimut plus pembrolizumab (Keytruda) against pembrolizumab monotherapy in previously untreated, unresectable or metastatic melanoma.2
The combination of imsapepimut and etimupepimut is an investigational, immune-modulatory therapeutic cancer vaccine candidate. Its mechanism of action is intended to stimulate activation and expansion of T cells against indoleamine 2,3-dioxygenase 1 (IDO1) positive and/or programmed death-ligand 1 (PD-L1) positive cells, targeting both tumor cells and immunosuppressive cells in the tumor microenvironment.1
The study enrolled treatment-naive adult patients from over 100 centers with histologically or cytologically confirmed stage 3 or stage 4 melanoma. Patients were excluded if they had known or suspected metastases or active disease in the central nervous system. A total of 407 patients were randomized 1:1 to receive either 200 mg of intravenous (IV) pembrolizumab every 3 weeks as monotherapy (n = 204), or 200 mg of IV pembrolizumab in combination with subcutaneous imsapepimut and etimupepimut (n = 203).
The study examined progression-free survival (PFS) as its primary end point, and overall survival, response measures, disease control rate, and safety and tolerability as secondary end points.
What Were the Study Findings?
Results from the overall study population yielded a median PFS of 19.4 months in the experimental arm compared with 11.0 months in the control arm, equating to a 23% reduction in the hazard of death in the experimental arm compared to the control arm (95.5% CI, 0.58–1.00).3 Moreover, in a subgroup analysis, the study demonstrated PFS improvement in subgroups with factors associated with poor prognosis. Specifically, a more pronounced effect was observed among patients with PD-L1–negative tumors who received the treatment combination, with a median PFS of 16.6 months (HR, 0.54; 95.5% CI, 0.35–0.85).
Ultimately, while these data suggest potential clinical benefit, the P-value of 0.056 for the primary end point in the overall study population fell outside of the study’s statistical significance threshold of P ≤.045.
Regarding safety, the treatment combination was observed to be well-tolerated in the patient population, with no new safety signals.
What Are the Sponsor’s Next Directions?
With this feedback from the FDA, IO Biotech has announced it intends to continue correspondence with the FDA for alignment on design for a potential new registrational study. Additionally, they plan to advance the IOB-013 data into the European regulatory space to begin conversations concerning submission in the European Union.
REFERENCES:
1. IO Biotech Provides Update Following Pre-BLA Meeting with FDA. News release. IO Biotech. September 29, 2025. Accessed October 2, 2025. https://tinyurl.com/d3drwzrx
2. IO102-IO103 in Combination With Pembrolizumab Versus Pembrolizumab Alone in Advanced Melanoma (IOB-013 / KN-D18). ClinicalTrials.gov. Updated August 28, 2025. Accessed October 2, 2025.https://clinicaltrials.gov/study/NCT05155254
3. 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. News release. IO Biotech. August 11, 2025. Accessed October 2, 2025.https://tinyurl.com/4a4w9vep
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