Sonesitatug vedotin reduced the risk of death by 42% in 2nd- and later-line CLDN18.2-positive advanced gastric/GEJ cancers in CLARITY-Gastric01

Sone-Ve reduced the risk of death by 53% in 3rd- and later-line setting in primary endpoint

Consistent data across CLDN18.2 expression levels supports potential for expanded use in up to 60% of patients in this setting
 

Positive results from the CLARITY-Gastric01 global Phase III trial showed AstraZeneca’s sonesitatug vedotin (Sone-Ve) demonstrated a statistically significant and highly clinically meaningful improvement in overall survival (OS) in 2nd- and later-line Claudin 18.2-positive advanced gastric cancers versus investigator’s choice of therapy.

The trial included patients with locally advanced or metastatic gastric cancer, gastroesophageal junction (GEJ) cancer, or oesophageal adenocarcinoma (EAC) with Claudin 18.2 (CLDN18.2) expression on at least 25% of tumour cells at any staining intensity, expanding the patient population beyond the current definition of CLDN18.2 positivity.

The results will be presented today during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain (abstract #LBA7).¹

The trial had dual primary endpoints of OS in the 3rd- and later-line treatment setting and progression-free survival (PFS) in the overall trial population of patients treated in the 2nd- and later-line setting. OS in the overall trial population was a key secondary endpoint.

In a planned interim analysis, Sone-Ve reduced the risk of death by 42% compared to investigator’s choice of therapy (based on an OS hazard ratio [HR] of 0.58; 95% confidence interval [CI] 0.47–0.73; p<0.000004) in the overall trial population. Median OS was 10.6 months for patients treated with Sone-Ve compared to 6.4 months for investigator’s choice of therapy.

In the 3rd- and later-line setting, Sone-Ve reduced the risk of death by 53% compared to investigator’s choice of therapy (OS HR 0.47; 95% CI 0.36–0.62; p<0.000001). Median OS doubled for patients treated with Sone-Ve (10.0 versus 5.0 months). The OS benefit observed was consistent across most predefined subgroups in both the overall trial population and the 3rd- and later-line setting, including subgroups based on CLDN18.2 expression levels (≥25%-<75% and ≥75%).

For the other dual primary endpoint of PFS as assessed by blinded independent central review (BICR) in the overall trial population, results showed a trend toward improved PFS in patients treated in the 2nd- and later-line setting but did not reach statistical significance. An exploratory analysis of investigator-assessed PFS showed a more pronounced treatment effect (PFS HR 0.59; 95% CI 0.48-0.73) that was consistent with observed OS results in this setting.

Rui-Hua Xu, M.D., Ph.D., Professor in the Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China, and principal investigator of the trial said: “These are remarkable survival results for Sone-Ve in 2nd- and later-line metastatic gastric cancer, a disease where patients face a poor prognosis once initial therapy fails. As the first CLDN18.2-targeted therapy to show survival benefit in this setting, extending median survival by more than four months compared to investigator's choice of therapy, Sone-Ve could transform the treatment paradigm for patients with CLDN18.2 expression.”

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “Sone-Ve has set a new benchmark for survival in 2nd- and later-line metastatic gastric cancer, and these data support expanding this precision treatment to a much broader population of patients with Claudin 18.2 expression. Sone-Ve could replace traditional chemotherapy-based regimens as a new standard of care in this setting, and these unprecedented data reinforce our confidence in its potential across CLDN18.2-positive cancers."

Summary of results: CLARITY-Gastric01ⁱ

The tolerability profile of Sone-Ve was manageable and consistent with its known safety profile with no new safety signals identified. Fewer Grade 3 or higher treatment-related adverse events (TRAEs) occurred in patients treated with Sone-Ve compared with the comparator arm (36.4% versus 44.8% of patients).

Sone-Ve is also being evaluated in the CLARITY-Gastric02 Phase III trial in combination with capecitabine, with or without rilvegostomig, as a 1st-line treatment for advanced or metastatic gastric cancer, GEJ cancer and EAC. In Phase II development, Sone-Ve is being evaluated in patients with advanced solid tumours in multiple combinations across settings, including in CLDN18.2-positive pancreatic and biliary tract cancers (BTC).

Notes

Gastric and GEJ cancers
Gastric (stomach) cancer is the fifth most common cancer worldwide and the fifth-leading cause of cancer-related death.² Nearly one million new patients were diagnosed with gastric cancer in 2024, with approximately 650,000 deaths reported globally. In many regions, its incidence has been increasing in patients younger than 50 years old, along with other gastrointestinal (GI) malignancies.²

GEJ cancer is a type of gastric cancer that arises from and spans the area where the oesophagus connects to the stomach.³

The majority of patients with gastric/GEJ cancers are diagnosed at an advanced or metastatic stage, where the prognosis is especially poor and treatment options are limited, with less than 20% surviving more than one year.^4,5 Most advanced gastric cancer patients will eventually experience disease progression after standard 1st-line therapies, and subsequent lines yield poor outcomes, with median survival of 5-10 months for patients receiving 2nd- and later-line systemic treatments.^6-8

CLDN18.2 has emerged as an important therapeutic target for these patients, with an estimated 60% of gastric/GEJ cancers expressing CLDN18.2 in 25% or more of tumour cells.⁹ Each year, there are roughly 183,500 patients in the US, EU, China and Japan treated in the 2nd- and later-line setting for advanced or metastatic CLDN18.2-positive, non-HER2-positive gastric/GEJ cancers.¹⁰

CLARITY-Gastric01
CLARITY-Gastric01 is a randomised, open-label, sponsor-blinded, multicentre, global Phase III trial evaluating Sone-Ve as a 2nd- and later-line therapy for patients with advanced or metastatic gastric cancer, GEJ cancer, or EAC with CLDN18.2 expression in 25% or more of tumour cells, with IHC+ of any intensity. In the trial, patients were randomised 1:1:1 in Stage 1 (dose selection) to Sone-Ve monotherapy 2.2 mg/kg or 1.8 mg/kg every three weeks, or investigator’s choice of therapy (including regionally accepted chemotherapies or targeted therapies), the comparator arm. In Stage 2, the trial continued with Sone-Ve 2.2 mg/kg as the recommended Phase III dose.

The efficacy analyses from this study will also provide the basis to evaluate the clinical performance of the Ventana SP455 assay for the identification of patients with advanced or metastatic gastric, GEJ or EAC cancers expressing CLDN18.2 who may benefit from Sone-Ve.

The trial is being conducted in 175 centres across 19 countries, including in North America, Europe, South America and Asia. Its dual primary endpoints are PFS as assessed by BICR in the 2nd- and later-line setting and OS in the 3rd- and later-line setting. A key secondary endpoint is OS in the 2nd- and later-line setting.

Sonesitatug Vedotin (Sone-Ve)
Sone-Ve is a potential global first-in-class investigational antibody drug conjugate (ADC) targeting CLDN18.2, a protein found in the stomach lining and a validated therapeutic target in oncology, particularly for GI cancers. Sone-Ve consists of an anti-CLDN18.2 monoclonal antibody, a protease-degradable linker and a cytotoxic small molecule MMAE payload.

Sone-Ve has received Orphan Drug Designation from the US Food and Drug Administration and the European Commission for the treatment of gastric and GEJ cancers. It has also received Breakthrough Designation in China for the 2nd-line treatment of gastric cancer.

AstraZeneca entered into a global exclusive licence agreement with KYM Biosciences to develop and commercialise Sone-Ve in March 2023. The Company recently announced a clinical collaboration agreement with Summit Therapeutics to evaluate Sone-Ve in combination with ivonescimab, a first-in-class PD-1/VEGF bispecific, in GI cancers.

AstraZeneca in GI cancers
AstraZeneca has a broad development programme for the treatment of GI cancers across several medicines and a variety of tumour types and stages of disease. In 2024, GI cancers collectively represented approximately 5 million new cancer cases leading to approximately 3.3 million deaths.¹¹

Within this programme, the Company is committed to improving outcomes in gastric, liver, biliary tract, oesophageal, pancreatic and colorectal cancers.

Imfinzi (durvalumab), an anti-PDL1 antibody, is approved in the US, China, EU, Japan and other countries in combination with chemotherapy in locally advanced or metastatic BTC, in combination with Imjudo (tremelimumab) in unresectable hepatocellular carcinoma (HCC) and in combination with FLOT chemotherapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel) in early-stage and locally advanced gastric and GEJ cancers. Imfinzi is also approved as a monotherapy in unresectable HCC in Japan, China and the EU.

Enhertu (trastuzumab deruxtecan), a HER2-directed ADC, is approved in the US, China, EU, Japan and several other countries for HER2-positive advanced gastric cancer. Enhertu is jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Lynparza (olaparib), a first-in-class PARP inhibitor, is approved in the US and several other countries for the treatment of BRCA-mutated metastatic pancreatic cancer. Lynparza is developed and commercialised in collaboration with MSD (Merck & Co., Inc. inside the US and Canada).

Orpathys (savolitinib), an oral, potent, and highly selective MET tyrosine kinase inhibitor (TKI), has received conditional approval in China for the treatment of patients with locally advanced or metastatic gastric cancer or GEJ adenocarcinoma harbouring MET amplification who have progressed on at least two prior lines of systemic therapy. Orpathys is being jointly developed and commercialised by AstraZeneca and HUTCHMED.

The Company is also assessing rilvegostomig, a PD-1/TIGIT bispecific antibody, in combination with chemotherapy as an adjuvant therapy in BTC, and in combination with Enhertu in previously untreated, HER2-expressing, locally advanced or metastatic BTC. Rilvegostomig is also being evaluated in combination with bevacizumab with or without Imjudo as a 1st-line treatment in patients with advanced HCC, and as a 1st-line combination treatment in patients with HER2-positive, or CLDN18.2-positive and HER2-negative, locally advanced unresectable or metastatic gastric and GEJ cancers.

In addition to Sone-Ve, AstraZeneca is also advancing AZD5863, a novel CLDN18.2/CD3 T-cell engager bispecific antibody licensed from Harbour Biomed in Phase I development.

In early development, AstraZeneca is developing AZD7003, a Glypican 3 armoured CAR T, in HCC. The Company is also advancing a pan-KRAS inhibitor programme licensed from Jacobio Pharma, which is being evaluated in Phase I trials in advanced solid tumours with KRAS alterations, including in pancreatic ductal adenocarcinoma.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Disease, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Social Media @AstraZeneca.

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