WILMINGTON, DE — AstraZeneca’s experimental antibody-drug conjugate sonesitatug vedotin improved overall survival in a Phase III trial of previously treated CLDN18.2-positive advanced gastric and related cancers, potentially broadening targeted treatment to patients with lower levels of the biomarker.
The CLARITY-Gastric01 study met its primary overall-survival endpoint in patients receiving third-line or later treatment and a key secondary survival endpoint across the broader second-line or later population, AstraZeneca reported.
The trial did not meet its other primary endpoint. Progression-free survival showed a favorable trend but failed to reach statistical significance in the overall population, according to the company.
Detailed survival figures, including median overall survival, hazard ratios and statistical values, were not included in the high-level results. AstraZeneca plans to present the data at a medical meeting and submit them to regulatory authorities.
The study evaluated sonesitatug vedotin against an investigator-selected therapy in patients with locally advanced or metastatic gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma. Eligible tumors expressed CLDN18.2 on at least 25% of cells at any staining intensity.
That threshold could expand the addressable population beyond higher-expression groups used in some CLDN18.2 treatment strategies. AstraZeneca estimates approximately 60% of gastric and gastroesophageal junction cancers meet the trial’s expression threshold.
Sonesitatug vedotin is designed to deliver the cytotoxic agent monomethyl auristatin E directly to cells expressing CLDN18.2. AstraZeneca described the drug as a potential first-in-class CLDN18.2-targeted antibody-drug conjugate.
“Sone-Ve is the first CLDN18.2-targeted antibody drug conjugate to demonstrate an overall survival benefit in this setting,” principal investigator Rui-Hua Xu stated. He characterized the results as a potential basis for a precision treatment reaching a broader CLDN18.2-positive population.
The company reported that the treatment was well tolerated and that its safety findings were consistent with the drug’s established profile, with no new safety signals identified. The release did not provide rates of serious adverse events, treatment discontinuations or treatment-related deaths.
CLARITY-Gastric01 enrolled patients at 175 centers in 19 countries across North America, Europe, South America and Asia. Participants were assigned to sonesitatug vedotin or an investigator’s choice of therapy, with 2.2 milligrams per kilogram every three weeks selected as the Phase III dose.
AstraZeneca licensed global development and commercialization rights to sonesitatug vedotin from KYM Biosciences in March 2023.
The drug is also being studied in first-line advanced gastric and gastroesophageal junction cancers and in other CLDN18.2-positive tumors, including pancreatic and biliary tract cancers.
Sonesitatug vedotin has orphan-drug designations from the U.S. Food and Drug Administration and European Commission for gastric and gastroesophageal junction cancers, along with breakthrough designation in China for second-line gastric cancer.
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