WILMINGTON, Del. — AstraZeneca announced positive results from a global Phase 3 clinical trial showing that its experimental cancer drug sonesitatug vedotin (Sone-Ve) reduced the risk of death by 42% in patients with previously treated, advanced gastric and related cancers compared with existing treatment options.
The findings from the CLARITY-Gastric01 trial demonstrated a statistically significant improvement in overall survival among patients with advanced or metastatic gastric cancer, gastroesophageal junction (GEJ) cancer or esophageal adenocarcinoma whose tumors express the Claudin 18.2 (CLDN18.2) protein.
The results were presented at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain.
In the overall study population, which included patients receiving second-line or later treatment, those treated with Sone-Ve achieved a median overall survival of 10.6 months, compared with 6.4 months for patients receiving therapies selected by their physicians.
The treatment demonstrated an even greater survival benefit among patients receiving third-line or later therapy, reducing the risk of death by 53%. Median overall survival in this group doubled to 10 months with Sone-Ve, compared with five months for patients receiving other treatments.
The study involved 532 patients in the second-line and later treatment population, including 355 patients receiving third-line or later therapy. It was conducted across 175 clinical centers in 19 countries spanning North America, Europe, South America and Asia.
Sone-Ve is an investigational antibody-drug conjugate designed to target CLDN18.2, a protein expressed in certain gastrointestinal cancers. The therapy combines an antibody targeting the protein with a cancer-killing drug intended to deliver treatment directly to tumor cells.
The trial included patients whose tumors expressed CLDN18.2 in at least 25% of cancer cells, broadening the population beyond the more restrictive expression thresholds used in some existing targeted treatment approaches.
AstraZeneca said the survival benefits were generally consistent across predefined patient subgroups, including those with different levels of CLDN18.2 expression.
“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,” said Dr. 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.
“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 added.
Although the trial met its primary endpoint for overall survival in patients receiving third-line or later treatment, it did not achieve statistical significance for its other primary endpoint, progression-free survival in the overall study population.
Median progression-free survival, as assessed by an independent central review, was 4.2 months for patients receiving Sone-Ve, compared with 3.8 months for those receiving other therapies.
However, an exploratory analysis based on investigator assessments showed median progression-free survival of 4.4 months with Sone-Ve, compared with three months in the comparator group.
The drug’s safety profile was consistent with previous findings, with no new safety concerns identified.
Severe or higher-grade treatment-related adverse events occurred in 36.4% of patients receiving Sone-Ve, compared with 44.8% of patients receiving other treatments.
Susan Galbraith, executive vice president of oncology hematology research and development at AstraZeneca, said the findings could support the development of new treatment options for a broader population of patients with advanced gastric cancer.
“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,” Galbraith said.
“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,” she added.
Gastric cancer is the fifth most common cancer worldwide and the fifth-leading cause of cancer-related deaths. Nearly one million new cases were diagnosed globally in 2024, with approximately 650,000 deaths reported.
Patients with advanced or metastatic gastric cancer often face limited treatment options, particularly after their disease progresses following initial therapy.
AstraZeneca estimates that approximately 60% of gastric and GEJ cancers express CLDN18.2 in at least 25% of tumor cells, potentially making a substantial proportion of patients candidates for targeted therapies.
Sone-Ve is also being evaluated in the Phase 3 CLARITY-Gastric02 trial as a potential first-line treatment for advanced or metastatic gastric cancer, GEJ cancer and esophageal adenocarcinoma.
Additional Phase 2 studies are investigating the drug in combination with other therapies for advanced solid tumors, including CLDN18.2-positive pancreatic and biliary tract cancers.
The investigational treatment has received Orphan Drug Designation from the U.S. Food and Drug Administration and the European Commission for gastric and GEJ cancers, as well as Breakthrough Therapy Designation in China for second-line gastric cancer treatment.
AstraZeneca acquired global development and commercialization rights to Sone-Ve through a licensing agreement with KYM Biosciences in March 2023.
The company has also announced a clinical collaboration with Summit Therapeutics to evaluate Sone-Ve in combination with ivonescimab, an investigational bispecific antibody targeting PD-1 and VEGF, in gastrointestinal cancers.
Sone-Ve remains investigational, and further regulatory review would be required before it could become an approved treatment.
