On July 27, 2026, AstraZeneca announced positive high-level results from the global Phase 3 CLARITY-Gastric01 trial evaluating sonesitatug vedotin in previously treated patients with CLDN18.2-positive locally advanced or metastatic gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma.
According to the announcement, sonesitatug vedotin, also known as Sone-Ve, produced a statistically significant and highly clinically meaningful improvement in overall survival compared with investigator’s choice of therapy. The study included patients with locally advanced or metastatic gastric cancer, gastroesophageal junction cancer, or oesophageal adenocarcinoma whose tumours expressed CLDN18.2 in at least 25% of tumour cells at any staining intensity.
AstraZeneca described CLARITY-Gastric01 as the first Phase 3 trial to demonstrate an overall survival benefit with a CLDN18.2-targeted antibody-drug conjugate in this treatment setting.
“Sone-Ve has the potential to reshape the treatment of gastric cancer by replacing classic chemotherapy with this novel targeted antibody drug conjugate to improve outcomes for patients. These transformative results from the first Phase III readout for Sone-Ve, together with our broad development programme, highlight the potential for Sone-Ve to become an important new medicine in CLDN18.2-positive cancers,” said Susan Galbraith, Executive Vice President, Oncology Haematology R&D.
Expanding the CLDN18.2-Positive Population
The trial used a CLDN18.2 positivity threshold of expression in at least 25% of tumour cells at any staining intensity. AstraZeneca stated that the results provide an opportunity to expand CLDN18.2 positivity to this threshold, which the company estimates is met by approximately 60% of gastric and gastroesophageal junction cancers.
Rui-Hua Xu, MD, PhD, Professor in the Department of Medical Oncology at Sun Yat-Sen University Cancer Center and principal investigator of CLARITY-Gastric01, said:
“Metastatic gastric cancer is an aggressive disease with very limited options once patients progress after first-line treatment. Sone-Ve is the first CLDN18.2-targeted antibody drug conjugate to demonstrate an overall survival benefit in this setting and has the potential to establish a new precision treatment for a broader population of patients with CLDN18.2 expression.”
CLARITY-Gastric01 Trial Design
CLARITY-Gastric01 is a randomised, open-label, sponsor-blinded, multicentre, global Phase 3 trial being conducted in 175 centres across 19 countries in North America, Europe, South America and Asia.
Eligible patients had advanced or metastatic gastric cancer, gastroesophageal junction cancer, or oesophageal adenocarcinoma with CLDN18.2 expression in at least 25% of tumour cells, with immunohistochemical staining of any intensity.
During the dose-selection stage, patients were randomly assigned in a 1:1:1 ratio to receive:
- Sonesitatug vedotin at 2.2 mg/kg every three weeks
- Sonesitatug vedotin at 1.8 mg/kg every three weeks
- Investigator’s choice of therapy
The second stage of the trial continued with sonesitatug vedotin at 2.2 mg/kg as the recommended Phase 3 dose. The study’s efficacy analyses will also provide the basis for evaluating the clinical performance of the Ventana SP455 assay in identifying patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, or oesophageal adenocarcinoma expressing CLDN18.2 who may benefit from sonesitatug vedotin.
Read about Claudin 18.2 Expression in Gastroesophageal Adenocarcinoma on OncoDaily.
Overall Survival Endpoints Met
CLARITY-Gastric01 had two primary endpoints: overall survival among patients receiving treatment in the third-line or later setting and progression-free survival in the overall trial population receiving second-line or later treatment.
The trial met its primary overall survival endpoint in patients treated in the third-line or later setting.
Sonesitatug vedotin also demonstrated a statistically significant and highly clinically meaningful improvement in the key secondary endpoint of overall survival across the overall population treated in the second-line or later setting. For the other dual primary endpoint, progression-free survival assessed by blinded independent central review showed a trend favouring sonesitatug vedotin in the second-line or later population but did not reach statistical significance.
Safety Profile
AstraZeneca reported that sonesitatug vedotin was well tolerated. Its safety profile was consistent with the known safety profile of sonesitatug vedotin, and no new safety signals were identified. The trial data will be presented at a forthcoming medical meeting.
What Is Sonesitatug Vedotin?
Sonesitatug vedotin is a novel antibody-drug conjugate targeting CLDN18.2, a protein found in the stomach lining and a validated therapeutic target in oncology, particularly in gastrointestinal cancers.
The antibody-drug conjugate consists of an anti-CLDN18.2 monoclonal antibody, a protease-degradable linker and a cytotoxic monomethyl auristatin E payload. AstraZeneca describes sonesitatug vedotin as a potential global first-in-class CLDN18.2-targeted antibody-drug conjugate.
The company entered into a global exclusive licence agreement with KYM Biosciences to develop and commercialise the treatment in March 2023. Sonesitatug vedotin is also being investigated in the Phase 3 CLARITY-Gastric02 trial in combination with capecitabine, with or without rilvegostomig, as a first-line treatment for advanced or metastatic gastric cancer, gastroesophageal junction cancer and oesophageal adenocarcinoma.
In Phase 2 development, sonesitatug vedotin is being evaluated in patients with advanced solid tumours in multiple combinations across treatment settings, including CLDN18.2-positive pancreatic and biliary tract cancers.
Next Steps
The CLARITY-Gastric01 data will be presented at a forthcoming medical meeting and shared with global regulatory authorities. Sonesitatug vedotin has received Orphan Drug Designation from the US Food and Drug Administration and the European Commission for gastric and gastroesophageal junction cancers. It has also received Breakthrough Designation in China for the second-line treatment of gastric cancer.
Based on the announcement, CLARITY-Gastric01 is the first Phase 3 trial to demonstrate an overall survival benefit with a CLDN18.2-targeted antibody-drug conjugate in this previously treated patient population.
The full announcement is available on AstraZeneca’s official website.