IO Biotech Presents Phase 3 Results for Cylembio® plus KEYTRUDA® (pembrolizumab) in First-line Advanced Melanoma at ESMO 2025
IO Biotech (NASDAQ: IOBT) reported Phase 3 results for Cylembio plus KEYTRUDA in first-line advanced melanoma showing a clinically relevant median PFS of 19.4 months vs 11.0 months for pembrolizumab alone (HR 0.77; 95% CI 0.58–1.00; p=0.0558), narrowly missing the prespecified statistical threshold (p≤0.045).
Benefits favored the combination across most subgroups, notably PD-L1–negative (16.6 vs 3.0 months; HR 0.54), BRAFV600-mutated tumors (HR 0.60), and elevated LDH (HR 0.60). Safety was comparable with no increase in immune-mediated AEs or grade ≥3 treatment-related events.
IO Biotech (NASDAQ: IOBT) ha riportato i risultati di fase 3 per Cylembio più KEYTRUDA nel melanoma avanzato in prima linea, mostrando una mediana di PFS di 19,4 mesi rispetto a 11,0 mesi per il pembrolizumab da solo (HR 0,77; CI al 95% 0,58–1,00; p=0,0558), mancando di poco la soglia statistica prespecifata (p≤0,045).
Benefici hanno favorito la combinazione nella maggior parte dei sottogruppi, in particolare PD-L1–negativo (16,6 vs 3,0 mesi; HR 0,54), tumori BRAFV600-mutati (HR 0,60) e LDH elevato (HR 0,60). La sicurezza era comparabile, senza aumento degli eventi avversi immuno-mediati o di grado ≥3 legati al trattamento.
IO Biotech (NASDAQ: IOBT) informó resultados de fase 3 para Cylembio más KEYTRUDA en melanoma avanzado en primera línea, mostrando una mediana de PFS de 19,4 meses frente a 11,0 meses para pembrolizumab solo (HR 0,77; IC del 95% 0,58–1,00; p=0,0558), quedando muy cerca de superar el umbral estadístico predefinido (p≤0,045).
Los beneficios favorecieron la combinación en la mayoría de los subgrupos, especialmente PD-L1–negativo (16,6 vs 3,0 meses; HR 0,54), tumores con BRAFV600 mutado (HR 0,60) y LDH elevada (HR 0,60). La seguridad fue comparable, sin aumento de eventos adversos inmunomediados o de grado ≥3 relacionados con el tratamiento.
IO Biotech (NASDAQ: IOBT)는 1차 치료 고도 악성 흑색종에서 Cylembio와 KEYTRUDA의 3상 결과를 발표했으며, pembrolizumab 단독 대비 임상적으로 중요한 중간 무진행생존기간(PFS) 19.4개월 vs 11.0개월를 보였다(HR 0.77; 95% CI 0.58–1.00; p=0.0558), 미리 설정된 통계적 임계값(p≤0.045)을 근소하게 벗어났다.
대부분의 하위군에서 조합의 이점이 관찰되었으며, 특히 PD-L1 음성 (16.6 vs 3.0개월; HR 0.54), BRAFV600 변이 종양(HR 0.60), LDH 상승(HR 0.60)에서 두드러졌다. 안전성은 면역 매개 부작용이나 등급 ≥3의 치료 관련 사건 증가 없이 비교가능했다.
IO Biotech (NASDAQ: IOBT) a annoncé les résultats de la phase 3 pour Cylembio plus KEYTRUDA dans le mélanome avancé en première ligne, montrant une médiane de PFS de 19,4 mois contre 11,0 mois pour le pembrolizumab seul (HR 0,77; IC à 95% 0,58–1,00; p=0,0558), manquant de peu le seuil statistique prédéfini (p≤0,045).
Les bénéfices ont été observés dans la plupart des sous-groupes, notamment PD-L1–négatif (16,6 contre 3,0 mois; HR 0,54), tumeurs BRAFV600 mutées (HR 0,60) et LDH élevé (HR 0,60). La sécurité était comparable, sans augmentation des effets indésirables immuno-médIés ou des événements liés au traitement de grade ≥3.
IO Biotech (NASDAQ: IOBT) berichtete Phase-3-Ergebnisse zu Cylembio plus KEYTRUDA bei erstlinien Behandlungsbeginn im fortgeschrittenen Melanom, die eine klinisch relevante Median-PFS von 19,4 Monaten gegenüber 11,0 Monaten für Pembrolizumab allein zeigen (HR 0,77; 95% KI 0,58–1,00; p=0,0558), und damit knapp den vordefinierten statistischen Grenzwert verfehlend (p≤0,045).
Die Vorteile lagen in der Mehrzahl der Subgruppen zugunsten der Kombination, insbesondere PD-L1–negativ (16,6 vs 3,0 Monate; HR 0,54), BRAFV600-mutierte Tumore (HR 0,60) und erhöhter LDH (HR 0,60). Die Sicherheit war vergleichbar, ohne Zunahme immunvermittelter AEs oder grad ≥3 behandlungsbezogener Ereignisse.
IO Biotech (NASDAQ: IOBT) أعلنت نتائج المرحلة 3 لـ Cylembio مع KEYTRUDA في الملعان الأولي في الورم الخبيث المتقدم، موضحة متوسط PFS قدره 19.4 شهرًا مقابل 11.0 شهرًا لبِمِوبروليزوماب وحده (HR 0.77؛ فاصل الثقة 95% 0.58–1.00؛ p=0.0558)، مع فشل بسيط في العتبة الإحصائية المحددة مسبقاً (p≤0.045).
فوائد المجموعة امتدت عبر معظم المجموعات الفرعية، لا سيما PD-L1–سلبي (16.6 مقابل 3.0 أشهر؛ HR 0.54)، الأورام BRAFV600 المتحورة (HR 0.60) وارتفاع LDH (HR 0.60). الأمان كان متماثلاً دون زيادة في الأحداث الضائرة المناعية أو أحداث مرتبطة بالعلاج من الدرجة ≥3.
IO Biotech (NASDAQ: IOBT) 报告了 Cylembio 加 KEYTRUDA 在一线晚期黑色素瘤中的 III 期结果，显示一个临床相关的中位无进展生存期(PFS) 19.4 个月对比 11.0 个月，相对于单用 pembrolizumab（HR 0.77；95% 可信区间 0.58–1.00；p=0.0558），略低于预设的统计阈值（p≤0.045）。
该组合在大多数亚组中获益，尤其是PD-L1–阴性（16.6 vs 3.0 个月；HR 0.54）、BRAFV600 突变肿瘤（HR 0.60）和 LDH 升高（HR 0.60）。安全性与单药相比相当，未见免疫介导的不良事件或三级及以上治疗相关事件的增加。
- Median PFS +8.4 months (19.4 vs 11.0 months)
- PD-L1–negative subgroup mPFS 16.6 vs 3.0 months
- Post-hoc mPFS 24.8 vs 11.0 months excluding prior anti-PD-1
- No increase in immune-mediated AEs (34.0% vs 38.4%)
- Primary endpoint narrowly missed statistical significance (p=0.0558)
- Overall HR 0.77 did not meet prespecified p≤0.045 threshold
- Phase 2 NSCLC mPFS modest at 8.1 months (21.4-month follow-up)
Insights
Phase 3 showed a clinically meaningful PFS gain but narrowly missed the pre-specified significance threshold.
The trial enrolled 407 previously untreated advanced melanoma patients and reported median PFS of 19.4 months with Cylembio plus pembrolizumab versus 11.0 months with pembrolizumab alone (HR 0.77; 95% CI, 0.58–1.00; p=0.0558). The magnitude of the absolute mPFS difference and consistent subgroup benefits—most notably in PD-L1–negative patients (16.6 vs 3.0 months; HR 0.54)—support a real clinical effect despite missing the prespecified alpha. The safety profile showed no increase in immune-mediated events or grade ≥3 treatment-related events, and vaccine-site reactions were mostly grade 1/2.
Key dependencies and risks include the statistical miss against the prespecified
Results strengthen scientific rationale but create regulatory and commercial ambiguity due to the narrow statistical miss.
The combination expanded IDO1‑ and PD‑L1–specific T‑cell responses and showed consistent PFS benefit across multiple subgroups, including BRAFV600‑mutated and patients with elevated LDH (HR 0.60). Safety parity with pembrolizumab alone reduces a key barrier for adoption and supports further development across indications; Phase 2 basket data in NSCLC and SCCHN reported modest mPFS values with encouraging durability and 18‑month OS signals.
Primary uncertainties are regulatory acceptance of a clinically meaningful but not statistically significant primary endpoint and the need for OS or additional controlled data to support approvals or label changes. Important near-term milestones to monitor are regulator feedback, any planned confirmatory studies or submission strategies, and publication or presentation of OS/mature endpoints at upcoming conferences over
- 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
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- Improvement in PFS favored the combination across virtually all subgroups, notably in patients with PD-L1-negative tumors, BRAFV600-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;
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;
The combination was well tolerated, with no increase in immune-mediated adverse events (
“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 ≥
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
FAQ
What were the Phase 3 IOB-013/KN-D18 results for IOBT (IOBT) in advanced melanoma?
How did Cylembio plus pembrolizumab perform in PD-L1–negative melanoma patients in the IOBT trial?
Did the combination of Cylembio and KEYTRUDA increase severe adverse events in the Phase 3 trial (IOBT)?
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What were the Phase 2 basket trial mPFS results for Cylembio plus KEYTRUDA in NSCLC and SCCHN?
