WILMINGTON, DE — AstraZeneca’s experimental cancer drug sonesitatug vedotin reduced the risk of death by 53% in patients receiving third-line or later treatment for advanced gastric and related cancers, according to Phase III trial results that could expand targeted treatment options for patients whose disease has progressed despite earlier therapies.
The CLARITY-Gastric01 trial found that median overall survival doubled to 10 months among patients receiving sonesitatug vedotin, known as Sone-Ve, compared with five months for those receiving treatments selected by their physicians.
The findings were presented at the European Society for Medical Oncology Congress 2026 in Madrid, Spain.
The global study evaluated patients with locally advanced or metastatic gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma whose tumors expressed the protein Claudin 18.2, or CLDN18.2.
The trial enrolled patients whose tumors showed CLDN18.2 expression in at least 25% of cancer cells, regardless of staining intensity. That threshold encompasses a broader population than the existing definition of CLDN18.2 positivity used for targeted treatment.
In the third-line and later treatment population, Sone-Ve produced an overall survival hazard ratio of 0.47, with a 95% confidence interval of 0.36 to 0.62 and a p-value below 0.000001.
The results indicate a statistically significant reduction in the risk of death compared with physician-selected treatment.
The survival benefit also extended to the broader study population, which included patients receiving second-line and subsequent therapies.
Across that group, median overall survival reached 10.6 months with Sone-Ve, compared with 6.4 months for patients receiving the investigator’s choice of treatment.
The corresponding hazard ratio was 0.58, representing a 42% reduction in the risk of death, with a 95% confidence interval of 0.47 to 0.73 and a p-value below 0.000004.
The survival advantage was generally consistent across predefined patient subgroups, including those with different levels of CLDN18.2 expression.
Patients whose tumors expressed the protein in 25% to less than 75% of cells showed a benefit, as did those with expression levels of at least 75%.
That consistency supports the potential use of Sone-Ve in a larger population of patients with advanced gastric and related cancers.
AstraZeneca estimates that the broader expression threshold could make as many as 60% of patients in this treatment setting potentially eligible for a CLDN18.2-directed approach.
The trial’s results were less definitive for progression-free survival, one of its two primary endpoints.
Progression-free survival, as assessed by blinded independent central review in the overall population receiving second-line or later treatment, showed a favorable trend but did not reach statistical significance.
An exploratory analysis based on investigators’ assessments found a progression-free survival hazard ratio of 0.59, with a 95% confidence interval of 0.48 to 0.73.
Although that analysis was consistent with the overall survival findings, it does not change the failure of the independently assessed progression-free survival endpoint to meet the trial’s statistical significance threshold.
The distinction is important because the study demonstrated a significant survival advantage without establishing a statistically significant improvement in its other primary endpoint.
Advanced gastric cancer remains difficult to treat after initial therapy fails, with subsequent treatment options frequently providing limited survival benefits.
Sone-Ve targets CLDN18.2, a protein expressed on the surface of certain cancer cells, allowing treatment to be directed toward tumors with that biological characteristic.
The results position the investigational therapy as a potential alternative to existing treatment regimens for patients whose tumors meet the trial’s biomarker criteria.
Rui-Hua Xu, professor of medical oncology at Sun Yat-Sen University Cancer Center in Guangzhou, China, and principal investigator of the trial, emphasized the importance of the survival improvement in patients with limited remaining treatment options.
“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,” Xu stated.
Susan Galbraith, AstraZeneca’s executive vice president of oncology and hematology research and development, indicated that the findings support investigating the drug across a broader range of patients with CLDN18.2-expressing cancers.
The company views Sone-Ve as a potential replacement for conventional chemotherapy-based regimens in later-line treatment, although the drug remains investigational.
The reported findings establish a statistically significant overall survival benefit in both the third-line and later population and the broader second-line and later population.
Further regulatory evaluation would determine whether Sone-Ve can become an approved treatment for patients with advanced CLDN18.2-expressing gastric, gastroesophageal junction and esophageal cancers.
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