Sone-Ve Cuts Death Risk 42% in Phase III Gastric Cancer Trial

AstraZeneca on 25 October 2026 announced positive results from the CLARITY-Gastric01 global Phase III trial, reporting that its investigational antibody drug conjugate sonesitatug vedotin (Sone-Ve) produced a statistically significant improvement in overall survival versus investigator’s choice of therapy in 2nd- and later-line CLDN18.2-positive advanced gastric cancers. In a planned interim analysis, Sone-Ve reduced the risk of death by 42% in the overall trial population, based on an overall-survival hazard ratio of 0.58, with median overall survival of 10.6 months for patients treated with Sone-Ve compared with 6.4 months for patients receiving investigator’s choice, according to the company’s announcement.

The results were scheduled for presentation the same day during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain, as abstract LBA7.

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

The interim analysis, with a data cut-off of 31 May 2026, covered 267 patients treated with Sone-Ve and 265 patients receiving investigator’s choice in the overall 2nd- and later-line population, among whom 139 and 174 deaths had occurred, respectively. The reported hazard ratio of 0.58 carried a 95% confidence interval of 0.47 to 0.73 and a p-value below 0.000004. Median overall survival was 10.6 months (95% CI 9.1–12.0) on Sone-Ve versus 6.4 months (95% CI 5.8–7.6) on the comparator, and the overall-survival rate at 12 months was 42.6% versus 27.8%.

In the 3rd- and later-line setting, which formed one of the trial’s dual primary endpoints, Sone-Ve reduced the risk of death by 53% versus investigator’s choice (hazard ratio 0.47; 95% CI 0.36–0.62; p<0.000001), the company reported. Median overall survival doubled, from 5.0 months on the comparator to 10.0 months on Sone-Ve, and the 12-month overall-survival rates were 38.1% and 18.1%, respectively. This population included 178 patients treated with Sone-Ve and 177 receiving investigator’s choice, with 85 and 122 deaths.

The other dual primary endpoint, progression-free survival as assessed by blinded independent central review in the overall trial population, did not reach statistical significance. Median progression-free survival was 4.2 months on Sone-Ve versus 3.8 months on investigator’s choice, with a hazard ratio of 0.77 (95% CI 0.62–0.96) and a p-value of 0.053193, which the company described as a trend toward improvement. An exploratory analysis of investigator-assessed progression-free survival showed a hazard ratio of 0.59 (95% CI 0.48–0.73), with medians of 4.4 and 3.0 months, a treatment effect the company said was consistent with the observed overall-survival results in this setting.

According to the announcement, the overall-survival benefit was consistent across most predefined subgroups in both the overall population and the 3rd- and later-line setting, including subgroups based on CLDN18.2 expression levels. The hazard ratio was 0.59 (95% CI 0.45–0.78) among patients with expression on at least 75% of tumour cells and 0.63 (95% CI 0.42–0.94) among those with expression on 25% to under 75% of tumour cells.

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

Rui-Hua Xu, professor in the Department of Medical Oncology at Sun Yat-Sen University Cancer Center in 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.” Xu described Sone-Ve as the first CLDN18.2-targeted therapy to show survival benefit in this setting, extending median survival by more than four months compared with investigator’s choice of therapy.

Susan Galbraith, Executive Vice President of Oncology Haematology R&D at AstraZeneca (AZN ), 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.” She added that Sone-Ve could replace traditional chemotherapy-based regimens as a new standard of care in this setting.

Trial Design and Patient Population

CLARITY-Gastric01 is a randomised, open-label, sponsor-blinded, multicentre, global Phase III trial evaluating Sone-Ve as a 2nd- and later-line therapy. In Stage 1, a dose-selection stage, patients were randomised 1:1:1 to Sone-Ve monotherapy at 2.2 mg/kg or 1.8 mg/kg every three weeks, or to investigator’s choice of therapy, which included regionally accepted chemotherapies or targeted therapies. In Stage 2, the trial continued with Sone-Ve 2.2 mg/kg as the recommended Phase III dose. The trial is being conducted in 175 centres across 19 countries, including in North America, Europe, South America, and Asia.

The trial’s dual primary endpoints are overall survival in the 3rd- and later-line setting and progression-free survival as assessed by blinded independent central review in the 2nd- and later-line setting, with overall survival in the 2nd- and later-line setting as a key secondary endpoint. According to the company, the efficacy analyses from the study will also provide the basis to evaluate the clinical performance of the Ventana SP455 assay for identifying patients with advanced or metastatic gastric, GEJ, or EAC cancers expressing CLDN18.2 who may benefit from Sone-Ve.

Disease Background and Development Programme

Gastric cancer is the fifth most common cancer worldwide and the fifth-leading cause of cancer-related death, with nearly one million new patients diagnosed and approximately 650,000 deaths globally in 2024, according to World Health Organization International Agency for Research on Cancer data cited in the announcement. GEJ cancer is a type of gastric cancer that arises from and spans the area where the oesophagus connects to the stomach. The announcement states that the majority of patients with gastric or GEJ cancers are diagnosed at an advanced or metastatic stage, where the prognosis is especially poor and less than 20% survive more than one year, and that median survival is 5 to 10 months for patients receiving 2nd- and later-line systemic treatments.

An estimated 60% of gastric and GEJ cancers express CLDN18.2 in 25% or more of tumour cells, according to the company. Roughly 183,500 patients each year in the US, EU, China, and Japan are treated in the 2nd- and later-line setting for advanced or metastatic CLDN18.2-positive, non-HER2-positive gastric or GEJ cancers.

The company describes Sone-Ve as a potential global first-in-class investigational antibody drug conjugate targeting CLDN18.2, a protein found in the stomach lining. The drug 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, and it has 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 has also announced a clinical collaboration agreement with Summit Therapeutics (SMMT ) to evaluate Sone-Ve in combination with ivonescimab, which it described as a first-in-class PD-1/VEGF bispecific, in gastrointestinal cancers.

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.