Cylembio plus pembrolizumab achieved a clinically relevant 19.4 months median progression free survival (mPFS) compared to 11.0 months mPFS with pembrolizumab alone; study narrowly missed progression free survival (PFS) primary endpoint for statistical significance
- Improvement in PFS favored the combination across virtually all subgroups, notably in patients with PD-L1-negative tumors, BRAF^V600-mutated tumors, and elevated LDH, without adding any systemic toxicity compared to pembrolizumab alone
Final data from the Phase 2 basket trial in lung and head & neck cancers also presented

NEW YORK, Oct. 20, 2025 (GLOBE NEWSWIRE) -- IO Biotech (NASDAQ:IOBT), a clinical-stage biopharmaceutical company developing novel, immune-modulatory, off-the-shelf therapeutic cancer vaccines, today presented detailed results from its global Phase 3 trial (IOB-013/KN-D18) of Cylembio^® (imsapepimut and etimupepimut, adjuvanted), in combination with Merck's (known as MSD outside the United States and Canada) anti-PD-1 therapy KEYTRUDA^® (pembrolizumab), for the first-line treatment of patients with unresectable or metastatic (advanced) melanoma. The data, presented as a proffered paper at the Melanoma and other skin tumors session of the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, expand upon topline results reported in August 2025.

Final results from the Phase 2 basket trial (IOB-022/KN-D38) evaluating Cylembio in combination with pembrolizumab in the first-line treatment of advanced non-small cell lung cancer (NSCLC) and recurrent/metastatic squamous cell carcinoma of head and neck (SCCHN) were also presented.

"The Phase 3 results in advanced melanoma, together with final data from our Phase 2 basket trial, continue to build on the encouraging clinical evidence seen with Cylembio in combination with anti-PD-1 therapy," said Mai-Britt Zocca, PhD, president and chief executive officer of IO Biotech. "These data reinforce Cylembio's potential to serve as a first-line treatment option across multiple tumor types, and we remain committed to advancing novel immune-modulatory vaccines that may help people living with cancer."

In the randomized Phase 3 trial, 407 patients with previously untreated advanced melanoma received either Cylembio plus pembrolizumab or pembrolizumab alone. Median progression-free survival was 19.4 months for the combination and 11.0 months for pembrolizumab (hazard ratio [HR] 0.77; 95% CI, 0.58–1.00; p=0.0558), narrowly missing the primary endpoint prespecified threshold for statistical significance (p≤0.045).

Across virtually all subgroups, outcomes in progression-free survival consistently favored the combination regimen, including among patients with PD-L1–negative tumors (16.6 vs 3.0 months; HR 0.54; 95% CI, 0.35-0.85), BRAF^V600 mutated tumors (HR 0.60; 95% CI, 0.40-0.90), and elevated LDH (HR 0.60; 95% CI, 0.39-0.92). In addition, a post-hoc analysis, excluding patients previously treated with anti-PD-1 therapy in neoadjuvant or adjuvant settings, showed mPFS of 24.8 months vs 11.0 months (HR 0.74; 95% CI, 0.56–0.98).

The combination was well tolerated, with no increase in immune-mediated adverse events (34.0% vs 38.4%) or grade ≥3 treatment-related events (14.5% vs 15.6%) compared to pembrolizumab alone. Local vaccine-related injection-site reactions, reported in 56% of patients in the exploratory arm, were generally mild and transient, mostly grade 1/2. IDO1- and PD-L1–specific T-cell responses were expanded in the vaccine arm versus the pembrolizumab arm, reinforcing the therapy's proposed immune-modulatory mechanism.

"Despite the narrow miss on statistical significance, I am encouraged by the clinically meaningful improvement in progression-free survival observed with IO102-IO103 plus pembrolizumab. The consistency of findings across subgroups, together with the manageable safety profile and convenient administration, supports continued exploration of IO102-IO103 as a potential option for patients. I am particularly excited about the encouraging outcomes seen in patients with PD-L1–negative tumors across multiple endpoints," said Jessica Hassel, MD, Professor at the Department of Dermatology and National Center for Tumor Diseases at the University Hospital Heidelberg, Germany, and lead enrolling investigator for the Phase 3 trial.

Phase 2 Basket Trial in NSCLC and SCCHN

Also presented at ESMO were final data from the Phase 2 basket trial (IOB-022/KN-D38), evaluating Cylembio in combination with pembrolizumab as first-line treatment for patients with NSCLC (PD-L1 TPS ≥50%) or SCCHN (PD-L1 CPS ≥20).

Among 49 efficacy-evaluable patients (31 with NSCLC and 18 with SCCHN), mPFS was 8.1 months at 21.4 months of follow-up in NSCLC and 7.0 months at 18 months of follow-up in SCCHN, with durable responses and encouraging 18-month overall survival (OS) rates. The combination's safety profile remained consistent with anti–PD-1 monotherapy, with no new safety signals.

The poster can be found on the "Posters & Publications" page of the IO Biotech website.

About Cylembio^®

Cylembio^® (imsapepimut and etimupepimut, adjuvanted) is an investigational, immune-modulatory, off-the-shelf therapeutic cancer vaccine candidate designed to kill both tumor cells and immune-suppressive cells in the tumor microenvironment (TME) by stimulating activation and expansion of T cells against indoleamine 2,3-dioxygenase 1 (IDO1) positive and/or programmed death-ligand 1 (PD-L1) positive cells. The company is currently conducting a pivotal Phase 3 trial (IOB-013/KN-D18; NCT05155254) investigating Cylembio in combination with Merck's anti-PD-1 therapy, KEYTRUDA^® (pembrolizumab) versus pembrolizumab alone in patients with advanced melanoma, a Phase 2 basket trial (IOB-022/KN-D38; NCT05077709) investigating Cylembio in combination with pembrolizumab as first line treatment in patients with advanced solid tumors, and a Phase 2 basket trial (IOB-032/PN-E40; NCT05280314) investigating Cylembio in combination with pembrolizumab as neo-adjuvant/adjuvant treatment of patients with solid tumors. Enrollment in the Phase 3 trial was completed rapidly by December 2023 with topline results from this trial reported in the third quarter of 2025. Enrollment in the two ongoing company-sponsored Phase 2 clinical trials is now complete.

The clinical trials are sponsored by IO Biotech and conducted in collaboration with Merck, which is supplying pembrolizumab. IO Biotech maintains global commercial rights to Cylembio.

Cylembio^® is a registered trademark of IO Biotech ApS, a subsidiary of IO Biotech.

KEYTRUDA^® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (known as MSD outside of the US and Canada).

About the IOB-013/KN-D18 Pivotal Phase 3 Clinical Trial

IOB-013/KN-D18 (ClinicalTrials.gov: NCT05155254) is an open label, randomized Phase 3 pivotal clinical trial evaluating Cylembio^® in combination with Merck's anti-PD-1 therapy, KEYTRUDA^® (pembrolizumab) versus pembrolizumab alone in patients with previously untreated, unresectable or metastatic (advanced) melanoma. Enrollment in the trial was completed by December 2023 with a total of 407 patients enrolled from more than 100 centers across the United States, Europe, Australia, Turkey, Israel and South Africa. The primary endpoint of the study was progression-free survival. Secondary endpoints include overall response rate, overall survival, durable objective response rate, complete response rate, duration of response, time to complete response, disease control rate, and incidence of adverse events and serious adverse events (safety and tolerability). Biomarkers in the blood and tumor tissue will also be assessed as exploratory endpoints. The company reported topline results from this trial in the third quarter of 2025. IO Biotech is sponsoring the Phase 3 trial and Merck is supplying pembrolizumab.

About IOB-022/KN-D38 Phase 2 Solid Tumor Basket Trial

IOB-022/KN-D38 (NCT05077709) is a non-comparative, open label trial to investigate the safety and efficacy of Cylembio^® in combination with Merck's anti-PD-1 therapy, KEYTRUDA^® (pembrolizumab) in the first-line treatment of metastatic non-small cell lung cancer (NSCLC) or recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) at sites in the United States, Spain, and the United Kingdom. IO Biotech is sponsoring the Phase 2 trial and Merck is supplying pembrolizumab.

About IO Biotech

IO Biotech is a clinical-stage biopharmaceutical company developing novel, immune-modulatory, off-the-shelf therapeutic cancer vaccines based on its T-win^® platform. The T-win platform is based on a novel approach to cancer vaccines designed to activate T cells to target both tumor cells and the immune-suppressive cells in the tumor microenvironment. IO Biotech is advancing its lead cancer vaccine candidate, Cylembio^®, in clinical trials, and additional pipeline candidates through preclinical development. IO Biotech is headquartered in Copenhagen, Denmark and has US headquarters in New York, New York.

For further information, please visit www.iobiotech.com. Follow us on our social media channels on LinkedIn and X (@IOBiotech).

Forward-Looking Statement

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements, including statements regarding the timing or outcome of communications with regulatory authorities including the FDA, the timing or outcome of the submission of marketing applications, including a BLA, for Cylembio, the timing or outcome of the launch of Cylembio, and statements regarding other current or future clinical trials, their timing, progress, enrollment or results, or the company's financial position or cash runway, are based on IO Biotech's current assumptions and expectations of future events and trends, which affect or may affect its business, strategy, operations or financial performance, and actual results and other events may differ materially from those expressed or implied in such statements due to numerous risks and uncertainties. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. Because forward-looking statements are inherently subject to risks and uncertainties, you should not rely on these forward-looking statements as predictions of future events. These forward-looking statements speak only as of the date hereof and should not be unduly relied upon. Except to the extent required by law, IO Biotech undertakes no obligation to update these statements, whether as a result of any new information, future developments or otherwise.

Contact:

Investors

Maryann Cimino, Director of Investor Relations

IO Biotech, Inc.

617-710-7305

mci@iobiotech.com

Media

Julie Funesti

Edelman

917-498-1967

julie.funesti@edelman.com

IO Biotech Presents Phase 3 Results for Cylembio® plus KEYTRUDA® (pembrolizumab) in First-line Advanced Melanoma at ESMO 2025