Ivonescimab Plus Chemotherapy Demonstrates Consistent Global Benefit: HARMONi Data Update Shows OS HR=0.78, Nominal P=0.0332
Summit Therapeutics (NASDAQ:SMMT) announced updated results from the global Phase III HARMONi trial for ivonescimab, a novel PD-1/VEGF bispecific antibody. The trial demonstrated an improved overall survival (OS) hazard ratio of 0.78 with a nominal p-value of 0.0332. The median OS was 16.8 months for ivonescimab plus chemotherapy versus 14.0 months for placebo plus chemotherapy.
Key findings include statistically significant progression-free survival (PFS) with a hazard ratio of 0.52 (p<0.00001), and higher overall response rates in the ivonescimab arm (45%) compared to placebo (34%). North American patients showed particularly strong results with an OS hazard ratio of 0.70. The drug demonstrated consistent benefits across Western and Asian populations, with a favorable safety profile.
Summit Therapeutics (NASDAQ:SMMT) ha reso noti i risultati aggiornati dello studio globale di Fase III HARMONi su ivonescimab, un nuovo anticorpo bispecifico PD-1/VEGF. Lo studio ha evidenziato un miglioramento della sopravvivenza globale (OS) con un hazard ratio di 0,78 (p nominale 0,0332). La mediana di OS è stata di 16,8 mesi con ivonescimab più chemioterapia contro 14,0 mesi con placebo più chemioterapia.
I risultati principali includono una progression-free survival (PFS) statisticamente significativa con hazard ratio 0,52 (p<0,00001) e tassi di risposta complessiva più elevati nel braccio ivonescimab (45%) rispetto al placebo (34%). I pazienti nordamericani hanno mostrato risultati particolarmente solidi con un OS HR di 0,70. Il farmaco ha fornito benefici coerenti in popolazioni occidentali e asiatiche, con un profilo di sicurezza favorevole.
Summit Therapeutics (NASDAQ:SMMT) anunció resultados actualizados del ensayo global de fase III HARMONi con ivonescimab, un novedoso anticuerpo biespecífico PD-1/VEGF. El estudio mostró una mejora en la supervivencia global (OS) con un hazard ratio de 0,78 y un valor p nominal de 0,0332. La mediana de OS fue de 16,8 meses con ivonescimab más quimioterapia frente a 14,0 meses con placebo más quimioterapia.
Entre los hallazgos clave figura una supervivencia libre de progresión (PFS) estadísticamente significativa con un hazard ratio de 0,52 (p<0,00001) y tasas de respuesta global superiores en el brazo de ivonescimab (45%) frente al placebo (34%). Los pacientes de Norteamérica mostraron resultados especialmente favorables con un HR de OS de 0,70. El fármaco demostró beneficios consistentes en poblaciones occidentales y asiáticas, con un perfil de seguridad favorable.
Summit Therapeutics (NASDAQ:SMMT)는 PD-1/VEGF 이중 특이 항체인 이보네시맙(ivonescimab)에 대한 글로벌 3상 HARMONi 시험의 업데이트 결과를 발표했습니다. 본 시험은 전체생존(OS) 위험비(hazard ratio) 0.78로 개선을 보였으며 명목상 p값은 0.0332였습니다. 중앙값 OS는 이보네시맙 병용 화학요법군에서 16.8개월, 위약 병용군에서 14.0개월이었습니다.
주요 결과로는 유의한 무진행생존(PFS) 개선(hazard ratio 0.52, p<0.00001)과 이보네시맙군의 전체 반응률이 45%로 위약군 34%보다 높았다는 점이 포함됩니다. 북미 환자군에서는 OS hazard ratio가 0.70으로 특히 강한 효과를 보였습니다. 약물은 서구 및 아시아 인구에서 일관된 이점을 보였고 안전성 프로파일도 양호했습니다.
Summit Therapeutics (NASDAQ:SMMT) a annoncé les résultats mis à jour de l'essai mondial de phase III HARMONi pour ivonescimab, un nouvel anticorps bispécifique PD‑1/VEGF. L'essai a montré une amélioration de la survie globale (OS) avec un hazard ratio de 0,78 et une valeur p nominale de 0,0332. La médiane d'OS était de 16,8 mois pour ivonescimab plus chimiothérapie contre 14,0 mois pour le placebo plus chimiothérapie.
Les résultats clés incluent une survie sans progression (PFS) statistiquement significative avec un hazard ratio de 0,52 (p<0,00001) et des taux de réponse globale supérieurs dans le bras ivonescimab (45%) comparé au placebo (34%). Les patients nord‑américains ont montré des résultats particulièrement solides avec un HR d'OS de 0,70. Le médicament a démontré des bénéfices cohérents dans les populations occidentales et asiatiques, avec un profil de sécurité favorable.
Summit Therapeutics (NASDAQ:SMMT) hat aktualisierte Ergebnisse der globalen Phase‑III‑Studie HARMONi zu ivonescimab, einem neuartigen PD‑1/VEGF‑bispezifischen Antikörper, veröffentlicht. Die Studie zeigte eine verbesserte Gesamtüberlebensrate (OS) mit einem Hazard Ratio von 0,78 bei einem nominalen p‑Wert von 0,0332. Die mediane OS betrug 16,8 Monate mit ivonescimab plus Chemotherapie gegenüber 14,0 Monaten mit Placebo plus Chemotherapie.
Zentrale Befunde sind eine statistisch signifikante progressionsfreie Überlebenszeit (PFS) mit einem Hazard Ratio von 0,52 (p<0,00001) sowie höhere Gesamtansprechraten im ivonescimab‑Arm (45%) gegenüber Placebo (34%). Nordamerikanische Patienten zeigten besonders starke Ergebnisse mit einem OS‑Hazard‑Ratio von 0,70. Das Medikament zeigte konsistente Vorteile in westlichen und asiatischen Populationen bei verträglichem Sicherheitsprofil.
- Overall survival hazard ratio improved to 0.78 with nominal p-value of 0.0332
- Statistically significant PFS with hazard ratio of 0.52 (p<0.00001)
- Higher overall response rate of 45% vs 34% for placebo
- Longer duration of response at 7.6 months vs 4.2 months for placebo
- Strong efficacy in North American patients with OS hazard ratio of 0.70
- Favorable safety and tolerability profile with no new safety signals
- Primary OS analysis did not achieve statistical significance at initial p-value threshold of 0.0448
Insights
Ivonescimab shows statistically significant survival benefits in lung cancer, strengthening its position as a potential breakthrough therapy.
The updated data from the global Phase III HARMONi trial demonstrates increasingly favorable overall survival outcomes for ivonescimab plus chemotherapy versus placebo plus chemotherapy. With longer follow-up of Western patients, the trial shows an overall survival hazard ratio of
What's particularly compelling is the consistency of benefit across geographical regions. The drug shows similar efficacy in both Western and Asian patients, which is relatively uncommon in oncology trials and suggests robust biological activity across diverse populations. The progression-free survival (PFS) data remains strong with a hazard ratio of
The objective response rate was
The dual PD-1/VEGF targeting mechanism appears to produce synergistic effects beyond what we typically see with single-target agents. Ivonescimab has now demonstrated superiority in four Phase III trials, including head-to-head comparisons against established standards of care. This consistent performance across multiple trials substantially reduces statistical uncertainty and builds a compelling case for this bispecific antibody's clinical utility.
- The overall survival (OS) hazard ratio (HR) in the HARMONi trial was 0.78, with a nominal p-value of 0.0332
- In the North American patients, the OS HR was 0.70
- The HARMONi trial has already demonstrated clinically meaningful and statistically significant progression-free survival (PFS) outcomes
- In the HARMONi trial, clinical endpoint benefits, including OS and PFS, were consistent across Western and Asian patient populations, and these results were also in alignment with the clinical data from the HARMONi-A trial conducted in
China
Longer-term follow-up of western patients showed improving, favorable trend in OS, yielding a hazard ratio (HR) of 0.78 and a nominal p-value of 0.0332.
Meanwhile, Akeso recently announced that the HARMONi-A study conducted in
The results from the first international multi-center Phase III HARMONi study of ivonescimab, along with those from the Phase III HARMONi-A study conducted in
Approximately
The trial results were presented by Jonathan Goldman, MD, Professor of Medicine at UCLA in the Hematology/Oncology Division, UCLA Director of Clinical Trials in Thoracic Oncology, Associate Director of Early Drug Development, and Chair of University of California Lung Cancer Consortium.
Clinically Meaningful Efficacy
As previously disclosed, ivonescimab in combination with chemotherapy showed a positive trend in OS in the primary analysis without achieving a statistically significant benefit with a hazard ratio of 0.79 (
In September 2025, an additional analysis was performed, whereby the western patients were followed to increase their time on study (Asian patients were locked at the time of the primary analysis). In this analysis that included longer-term follow-up of western patients (median follow-up time of western patients of 13.7 months), a hazard ratio consistent with the primary analysis was observed with an improved nominal p-value (HR=0.78;
As previously disclosed at the prespecified primary data analysis for PFS, ivonescimab in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement with a hazard ratio of 0.52 (
In a longer-term follow-up of PFS, which included all western patients and at least six months of follow-up time for all patients, ivonescimab plus chemotherapy demonstrated a consistent, clinically meaningful improvement in PFS with an observed HR of 0.57 (
Overall response rates were higher in the ivonescimab arm (
Ivonescimab demonstrated a favorable safety and tolerability profile with no new safety signals identified. The safety results from the HARMONi study were consistent with those observed in the HARMONi-A trial.
Ivonescimab has shown positive results in the HARMONi-2 trial, a randomized, double-blind, head-to-head Phase III study against pembrolizumab monotherapy, which led to its approval for first-line treatment of PD-L1-positive NSCLC (its second approved indication). Besides that, ivonescimab plus chemotherapy has now also demonstrated significant positive outcomes in another head-to-head Phase III study against tislelizumab plus chemotherapy in first-line squamous NSCLC. This clinical outcome demonstrates that ivonescimab shows significant clinical breakthroughs, whether compared to PD-1 monotherapy, or compared to PD-1 in combination with chemotherapy (the optimal standard of care for many cancer treatments), or compared to VEGF-related therapies in the area of anti-angiogenesis. This highlights the remarkable capability of ivonescimab to make leapfrog advancements in cancer treatment.
Ivonescimab continues to validate its clinically meaningful profile and potential with a strategically expanded development program targeting key immuno-oncology settings:
Phase III trials for Lung cancer (8 registrational/Phase III trials, 4 already met primary endpoints):
- First-line NSCLC, squamous and non-squamous (versus pembrolizumab + chemotherapy; global trial)
- First-line squamous NSCLC (versus tislelizumab + chemotherapy)
- NSCLC after progression on EGFR-TKI therapy (HARMONi-A and HARMONi studies)
- First-line PD-L1-positive NSCLC (versus pembrolizumab monotherapy)
- First-line PD-L1-high expressing NSCLC (versus pembrolizumab)
- IO-resistant NSCLC
- Consolidation therapy for limited-stage small cell lung cancer (LS-SCLC) without progression after concurrent chemoradiotherapy (cCRT)
Phase III trials for core immuno-oncology indications (first-line therapy):
- First-line biliary tract cancer (versus durvalumab + chemotherapy)
- First-line PD-L1-positive head and neck squamous cell carcinoma (HNSCC) in combination with ligufalimab (anti-CD47) versus pembrolizumab
Phase III trials for cold tumors and more：
- First-line triple-negative breast cancer (TNBC)
- First-line MSS/pMMR colorectal cancer (representing about
95% of CRC cases) - First-line pancreatic cancer
- Additional global Phase III trials are in advanced stages of planning
An extensive clinical foundation includes over 20 Phase II studies across more than 10 additional tumor types, generating compelling efficacy and safety data to enable rapid transition to further registrational studies worldwide.
Ivonescimab uniquely targets both PD-1 and VEGF, producing a synergistic anti-tumor effect. This dual mechanism not only combines the benefits of PD-1 and VEGF inhibition but also overcomes the efficacy and safety limitations of each target alone, resulting in pronounced clinical benefits. These advantages have been confirmed across multiple Phase III trials and real-world use, rapidly establishing ivonescimab as a next-generation leader in immunotherapy and anti-angiogenic therapy.
Akeso is implementing a dual-path strategy to maximize the value of ivonescimab world wide: accelerating domestic commercialization and label expansion in
Forward-Looking Statement of Akeso, Inc.
This announcement by Akeso, Inc. (9926.HK, "Akeso") contains "forward-looking statements". These statements reflect the current beliefs and expectations of Akeso's management and are subject to significant risks and uncertainties. These statements are not intended to form the basis of any investment decision or any decision to purchase securities of Akeso. There can be no assurance that the drug candidate(s) indicated in this announcement or Akeso's other pipeline candidates will obtain the required regulatory approvals or achieve commercial success. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.
Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in P.R.China, the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Akeso's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the Akeso's patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
Akeso does not undertake any obligation to publicly revise these forward-looking statements to reflect events or circumstances after the date hereof, except as required by law.
About Akeso
Akeso (HKEX: 9926.HK) is a leading biopharmaceutical company committed to the research, development, manufacturing and commercialization of the world's first or best-in-class innovative biological medicines. Founded in 2012, the company has created a unique integrated R&D innovation system with the comprehensive end-to-end drug development platform (ACE Platform) and bi-specific antibody drug development technology (Tetrabody) as the core, a GMP-compliant manufacturing system and a commercialization system with an advanced operation mode, and has gradually developed into a globally competitive biopharmaceutical company focused on innovative solutions. With fully integrated multi-functional platform, Akeso is internally working on a robust pipeline of over 50 innovative assets in the fields of cancer, autoimmune disease, inflammation, metabolic disease and other major diseases. Among them, 24 candidates have entered clinical trials (including 15 bispecific/multispecific antibodies and bispecific ADCs. Additionally, 7 new drugs are commercially available. Through efficient and breakthrough R&D innovation, Akeso always integrates superior global resources, develops the first-in-class and best-in-class new drugs, provides affordable therapeutic antibodies for patients worldwide, and continuously creates more commercial and social values to become a global leading biopharmaceutical enterprise.
For more information, please visit https://www.akesobio.com/en/about-us/corporate-profile/ and follow us on Linkedin.
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