IO Biotech Announces Clinical Improvement in Progression Free Survival Demonstrated in Pivotal Phase 3 Trial of Cylembio庐 plus KEYTRUDA庐 (Pembrolizumab) for the Treatment of First-line Advanced Melanoma, but Statistical Significance Narrowly Missed
IO Biotech (NASDAQ: IOBT) announced topline results from its pivotal Phase 3 trial of Cylembio庐 plus KEYTRUDA庐 for first-line advanced melanoma treatment. While the combination showed clinical improvement in progression-free survival (19.4 months vs. 11.0 months), it narrowly missed statistical significance with HR=0.77 (p=0.056).
Notable findings include a profound effect in PD-L1 negative patients (16.6 vs. 3.0 months, HR: 0.54, p=0.006) and improved results in patients without prior anti-PD-1 treatment (24.8 vs. 11.0 months, HR: 0.74, p=0.037). The combination demonstrated a positive safety profile with no new safety signals. A trend toward improved overall survival was observed (HR=0.79), though data is not yet mature.
IO Biotech plans to meet with the FDA this fall to discuss potential regulatory submission.
IO Biotech (NASDAQ: IOBT) ha annunciato i risultati principali della sua sperimentazione di fase 3 di Cylembio庐 pi霉 KEYTRUDA庐 come terapia di prima linea per il melanoma avanzato. Sebbene la combinazione abbia mostrato un miglioramento clinico nella sopravvivenza libera da progressione (19,4 mesi vs. 11,0 mesi), non ha raggiunto per poco la significativit脿 statistica con HR=0,77 (p=0,056).
Tra i riscontri pi霉 rilevanti un effetto marcato nei pazienti PD-L1 negativi (16,6 vs. 3,0 mesi, HR: 0,54, p=0,006) e risultati migliori nei pazienti senza precedente trattamento anti-PD-1 (24,8 vs. 11,0 mesi, HR: 0,74, p=0,037). La combinazione ha mostrato un profilo di sicurezza favorevole senza nuovi segnali di sicurezza. Si 猫 osservata una tendenza a un miglioramento della sopravvivenza globale (HR=0,79), ma i dati non sono ancora maturi.
IO Biotech intende incontrare la FDA questo autunno per discutere una possibile richiesta regolatoria.
IO Biotech (NASDAQ: IOBT) anunci贸 los resultados principales de su ensayo pivotal de fase 3 de Cylembio庐 m谩s KEYTRUDA庐 para el tratamiento de primera l铆nea del melanoma avanzado. Aunque la combinaci贸n mostr贸 una mejora cl铆nica en la supervivencia libre de progresi贸n (19,4 meses frente a 11,0 meses), qued贸 ligeramente por debajo de la significaci贸n estad铆stica con HR=0,77 (p=0,056).
Hallazgos notables incluyen un efecto marcado en pacientes PD-L1 negativos (16,6 vs. 3,0 meses, HR: 0,54, p=0,006) y mejores resultados en pacientes sin tratamiento previo anti-PD-1 (24,8 vs. 11,0 meses, HR: 0,74, p=0,037). La combinaci贸n mostr贸 un perfil de seguridad favorable sin nuevas se帽ales de riesgo. Se observ贸 una tendencia a la mejora de la supervivencia global (HR=0,79), aunque los datos a煤n no est谩n maduros.
IO Biotech planea reunirse con la FDA este oto帽o para discutir una posible presentaci贸n regulatoria.
IO Biotech (NASDAQ: IOBT)電� 1彀� 歆勴枆靹� 頋戩儔膦� 旃橂毳� 鞙勴暅 Cylembio庐鞕� KEYTRUDA庐 氤戩毄鞚� 頃奠嫭 3靸� 瓴瓣臣毳� 氚滍憸頄堨姷雼堧嫟. 氤戩毄鞖旊矔鞚� 氍挫頄夓儩臁搓赴臧勳棎靹� 鞛勳儊鞝� 臧滌劆鞚� 氤挫榾鞙茧倶 (19.4臧滌洈 vs. 11.0臧滌洈) 韱店硠鞝� 鞙犾潣靹膘棎電� 攴检爲頄堨毵� 氙鸽嫭頄堨姷雼堧嫟: HR=0.77 (p=0.056).
欤检殧 瓴瓣臣搿滊姅 PD-L1 鞚岇劚 頇橃瀽鞐愳劀鞚� 霘滊牱頃� 須臣(16.6 vs. 3.0臧滌洈, HR: 0.54, p=0.006)鞕� 鞚挫爠 頃�-PD-1 旃橂毳� 氚涭 鞎婌潃 頇橃瀽鞐愳劀鞚� 臧滌劆(24.8 vs. 11.0臧滌洈, HR: 0.74, p=0.037)鞚� 韽暔霅╇媹雼�. 氤戩毄鞖旊矔鞚� 靸堧鞖� 鞎堨爠靹� 鞁犿樃 鞐嗢澊 鞏戫樃頃� 鞎堨爠靹� 頂勲頃勳潉 氤挫榾鞀惦媹雼�. 鞝勳泊靸濎〈毳� 臧滌劆 瓴巾枼(HR=0.79)鞚� 甏�彀半悩鞐堨溂雮� 雿办澊韯半姅 鞎勳 靹膘垯頃橃 鞎婌晿鞀惦媹雼�.
IO Biotech電� 鞛犾灛鞝� 攴滌牅 鞝滌稖鞚� 雲检潣頃橁赴 鞙勴暣 鞚措矆 臧�鞚� FDA鞕� 須岇潣毳� 臧�歆� 鞓堨爼鞛呺媹雼�.
IO Biotech (NASDAQ: IOBT) a annonc茅 les r茅sultats principaux de son essai pivot de phase 3 茅valuant Cylembio庐 associ茅 脿 KEYTRUDA庐 en premi猫re ligne du m茅lanome avanc茅. Bien que la combinaison ait montr茅 une am茅lioration clinique de la survie sans progression (19,4 mois vs. 11,0 mois), elle n鈥檃 茅t茅 que l茅g猫rement en de莽脿 de la significativit茅 statistique avec HR=0,77 (p=0,056).
Points notables : un effet marqu茅 chez les patients PD-L1 n茅gatifs (16,6 vs. 3,0 mois, HR: 0,54, p=0,006) et de meilleurs r茅sultats chez les patients sans traitement anti-PD-1 ant茅rieur (24,8 vs. 11,0 mois, HR: 0,74, p=0,037). La combinaison a pr茅sent茅 un profil de s茅curit茅 favorable sans nouveaux signaux. Une tendance 脿 l鈥檃m茅lioration de la survie globale a 茅t茅 observ茅e (HR=0,79), mais les donn茅es ne sont pas encore matures.
IO Biotech pr茅voit de rencontrer la FDA cet automne pour discuter d鈥檜n 茅ventuel dossier r茅glementaire.
IO Biotech (NASDAQ: IOBT) gab die Topline-Ergebnisse seiner Phase-3-Studie zu Cylembio庐 plus KEYTRUDA庐 als Erstlinienbehandlung beim fortgeschrittenen Melanom bekannt. Zwar zeigte die Kombination eine klinische Verbesserung beim progressionsfreien 脺berleben (19,4 Monate vs. 11,0 Monate), verfehlte jedoch knapp die statistische Signifikanz mit HR=0,77 (p=0,056).
Bemerkenswerte Befunde sind ein deutlicher Effekt bei PD-L1-negativen Patienten (16,6 vs. 3,0 Monate, HR: 0,54, p=0,006) sowie bessere Ergebnisse bei Patienten ohne vorherige Anti-PD-1-Therapie (24,8 vs. 11,0 Monate, HR: 0,74, p=0,037). Die Kombination wies ein positives Sicherheitsprofil ohne neue Sicherheitsbedenken auf. Eine Tendenz zu verbessertem Gesamt眉berleben wurde beobachtet (HR=0,79), die Daten sind jedoch noch nicht ausgereift.
IO Biotech plant, sich diesen Herbst mit der FDA zu treffen, um eine m枚gliche Zulassungseinreichung zu besprechen.
- Significant PFS improvement in PD-L1 negative tumors (16.6 vs 3.0 months, HR: 0.54)
- Strong PFS benefit in patients without prior anti-PD-1 treatment (24.8 vs 11.0 months)
- Favorable safety profile with no new safety signals
- Positive trend in overall survival (HR=0.79)
- PFS improvement observed across virtually all subgroups
- Primary endpoint missed statistical significance threshold (p=0.056 vs required p鈮�0.045)
- Overall survival data not yet mature
- 56% of patients reported injection site reactions in combination arm
Insights
IO Biotech's melanoma treatment showed strong clinical benefit despite narrowly missing statistical significance, with notable PFS improvement in PD-L1 negative patients.
The Phase 3 trial results for Cylembio (imsapepimut and etimupepimut, adjuvanted) combined with pembrolizumab in first-line advanced melanoma reveal meaningful clinical improvements despite narrowly missing the pre-specified statistical threshold. The combination demonstrated a
The magnitude of benefit is clinically substantial - 19.4 months median PFS for the combination versus 11.0 months for pembrolizumab alone. This represents an 8.4-month absolute improvement, which is remarkable in advanced melanoma treatment where extending progression-free time is critically important.
Two findings are particularly noteworthy: First, in patients without prior anti-PD-1 exposure (n=371), the combination achieved 24.8 months median PFS versus 11.0 months (HR: 0.74, nominal p=0.037). Second, in PD-L1 negative patients - traditionally poor responders to immunotherapy - the combination showed dramatic benefit with 16.6 months median PFS versus just 3.0 months for pembrolizumab alone (HR: 0.54, nominal p=0.006).
The early separation and sustained duration of PFS curves suggests durable clinical benefit. While overall survival data isn't mature, the trend (HR: 0.79) is encouraging. The safety profile appears favorable, with injection site reactions being the primary adverse event, avoiding the systemic toxicity concerns that typically accompany novel combination regimens.
Despite missing statistical significance, the consistent benefit across subgroups, particularly in patients with poor prognostic factors, suggests Cylembio has meaningful clinical activity. The upcoming FDA discussions will be crucial - regulatory flexibility has been shown for therapies demonstrating substantial clinical benefit even when narrowly missing statistical thresholds, especially in areas of unmet need like PD-L1 negative melanoma patients.
- Patients treated with Cylembio (imsapepimut and etimupepimut, adjuvanted) plus pembrolizumab achieved improvement in progression free survival (PFS) compared to patients treated with pembrolizumab monotherapy, HR=0.77 (CI 0.58-1.00), (p=0.056), with median PFS (mPFS) of 19.4 months vs. 11.0 months, respectively; the results on the primary endpoint narrowly missed the study鈥檚 statistical significance threshold of p鈮�0.045
- In patients enrolled in this study without prior neo-adjuvant/adjuvant anti-PD-1 treatment (n=371), patients treated with Cylembio plus pembrolizumab achieved improvement in PFS, HR: 0.74 (CI 0.56-0.98) (nominal p=0.037), with mPFS of 24.8 months vs. 11.0 months for the control arm
- Improvement in PFS was achieved across virtually all subgroups, including those with poor prognostic factors
- A profound effect was observed in patients with PD-L1 negative tumors treated with Cylembio plus pembrolizumab, HR: 0.54 (CI 0.35-0.85) (nominal p=0.006), with mPFS of 16.6 months vs. 3.0 months for the control arm
- A trend towards improvement in overall survival (OS) was observed in patients treated with Cylembio plus pembrolizumab (OS not yet mature), HR=0.79 (CI 0.57-1.10)
- Cylembio plus pembrolizumab was well tolerated, with no new safety signals observed
- IO Biotech plans to meet with the FDA this fall to discuss the data and next steps for a potential regulatory submission
- Company to host conference call today at 8:30 a.m. ET to discuss these results
NEW YORK, Aug. 11, 2025 (GLOBE NEWSWIRE) -- IO Biotech (Nasdaq: IOBT) today announces topline results from the pivotal Phase 3 trial of its investigational, immune-modulatory, off-the-shelf therapeutic cancer vaccine, Cylembio庐 (imsapepimut and etimupepimut, adjuvanted). The trial evaluated Cylembio in combination with Merck鈥檚 anti-PD-1 therapy, KEYTRUDA庐 (pembrolizumab), vs. pembrolizumab alone as a first-line treatment in 407 patients with unresectable or metastatic (advanced) melanoma. In the study, Cylembio plus pembrolizumab demonstrated clinical improvement in progression free survival compared to pembrolizumab alone, but statistical significance was narrowly missed on the primary endpoint.
鈥淚n this study, we observed a highly encouraging improvement in progression free survival and consistent trend in overall survival in patients treated with Cylembio,鈥� said Mai-Britt Zocca, PhD, president and chief executive officer of IO Biotech. 鈥淭he 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.鈥�
The randomized, open-label study enrolled 407 patients across more than 100 sites worldwide. Patients received either Cylembio in combination with pembrolizumab (n=203) or pembrolizumab alone (n=204). The primary endpoint was PFS as assessed by a blinded independent review committee per RECIST v1.1. The early and sustained separation of PFS curves demonstrated an improvement with a hazard ratio of 0.77 [
Improvement in PFS was achieved across virtually all subgroups, including those with poor prognostic factors, with a profound effect in patients with PD-L1 negative tumors treated with Cylembio plus pembrolizumab (n=67) compared to patients treated with pembrolizumab monotherapy (n=63), HR: 0.54 (CI 0.35-0.85) (nominal p=0.006), with mPFS of 16.6 months vs. 3.0 months, respectively. Additionally, in a post hoc analysis of patients enrolled in this study without prior anti-PD-1 treatment (n=371), patients treated with Cylembio plus pembrolizumab achieved improvement in PFS compared to patients treated with pembrolizumab monotherapy, HR: 0.74 (CI 0.56-0.98) (nominal p=0.037), with mPFS of 24.8 months vs. 11.0 months, respectively.
The combination was well tolerated, with no new safety signals observed. Injection site reactions, which were transient and resolved on treatment, were the most commonly reported adverse events in the combination arm, with
鈥淚n this study, patients treated with Cylembio in combination with pembrolizumab have achieved the longest median PFS 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 PFS, compared to 3.0 months in patients treated with pembrolizumab alone,鈥� said Omid Hamid, MD, Director, Clinical Research and Immunotherapy at The Angeles Clinic and Research Institute, A Cedars Sinai Affiliate. 鈥淭he 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.鈥�
鈥淭hese data show the potential of a therapeutic cancer vaccine in patients with metastatic melanoma,鈥� 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. 鈥淲e 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.鈥�
鈥淒elaying progression and improving survival is the ultimate treatment goal for patients and although overall survival is not yet mature, the trend we are seeing in OS with separation of the curves is encouraging, with a consistent PFS clinical improvement and OS trend favoring the combination arm across virtually all subgroups, with no new safety signals or significant additional systemic toxicity,鈥� said Qasim Ahmad, MD, chief medical officer of IO Biotech. 鈥淲e are deeply grateful to the patients for their participation in this study, as well as to investigators and study coordinators whose dedication and collaboration brings us one step closer to delivering a new treatment option to patients in need.鈥�
鈥淪ince reporting the positive outcome of our Phase 1/2 study (MM1636) in a similar patient population, we have been eagerly awaiting these results supporting the activity of Cylembio combined with an anti-PD-1 in patients with advanced melanoma,鈥� said Inge Marie Svane, MD, PhD, Professor, Director of the National Center for Cancer Immune Therapy (CCIT) at the Copenhagen University Hospital, Herlev and Principal Investigator in the Phase 3 trial. 鈥淭hese data provide evidence that a therapeutic cancer vaccine can improve progression free survival in patients with metastatic disease.鈥�
Based on these results, IO Biotech plans to meet with the United States (US) Food and Drug Administration (FDA) this fall to discuss the totality of data and determine next steps for submission of a Biologics License Application (BLA) for the treatment of advanced melanoma. Additionally, the company plans to present more detailed results from the IOB-013 study at an upcoming medical meeting.
Conference Call and Webcast Information
IO Biotech management will hold a conference call and webcast today at 8:30 a.m. ET to discuss these clinical data results. Participants can register for the live webcast . The live webcast and replay will be available through IO Biotech鈥檚 website .
About the IOB-013/KN-D18 Pivotal Phase 3 Clinical Trial
IOB-013/KN-D18 (ClinicalTrials.gov: NCT05155254) was an open label, randomized Phase 3 pivotal clinical trial evaluating Cylembio庐 in combination with Merck鈥檚 anti-PD-1 therapy, KEYTRUDA庐 (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 Cylembio庐
Cylembio庐 (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鈥檚 anti-PD-1 therapy, KEYTRUDA庐 (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庐 is a registered trademark of IO Biotech ApS, a subsidiary of IO Biotech.
KEYTRUDA庐 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 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庐 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庐, 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.
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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 the FDA, submission of a BLA, the launch of Cylembio, and statements regarding other current or future clinical trials, their progress, enrollment or results, or the company鈥檚 financial position or cash runway, are based on IO聽Biotech鈥檚 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.
Contacts:
Investors
Maryann Cimino, Director of Investor Relations
IO Biotech, Inc.
617-710-7305
Media
Julie Funesti
Edelman
917-498-1967
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