CAMBRIDGE, UK, July 27, 2026
AstraZeneca has announced positive high-level results from the global Phase III CLARITY-Gastric01 trial, demonstrating that sonesitatug vedotin (Sone-Ve) achieved a statistically significant and highly clinically meaningful improvement in overall survival (OS) for patients with second-line and later CLDN18.2-positive advanced gastric cancer, gastroesophageal junction (GEJ) cancer, and oesophageal adenocarcinoma (EAC). The study represents the first Phase III clinical trial to demonstrate an overall survival benefit for an anti-CLDN18.2 antibody-drug conjugate (ADC) in this patient population and marks the first pivotal readout from AstraZeneca’s wholly owned ADC portfolio. The results also support expanding CLDN18.2 positivity to tumors with ≥25% expression, potentially making nearly 60% of patients with advanced CLDN18.2-positive gastric and GEJ cancers eligible for this targeted therapy. This breakthrough reinforces AstraZeneca’s growing leadership in precision oncology while highlighting the transformative potential of next-generation antibody-drug conjugates for difficult-to-treat gastrointestinal cancers.
CLARITY-Gastric01 Delivers Significant Overall Survival Benefit
The CLARITY-Gastric01 study evaluated Sone-Ve in patients with locally advanced or metastatic gastric cancer, GEJ cancer, or oesophageal adenocarcinoma whose tumors expressed CLDN18.2 in at least 25% of tumor cells. The randomized global Phase III trial successfully met its dual primary endpoint of overall survival in third-line and later treatment, while also achieving the key secondary endpoint of overall survival in the broader second-line and later treatment population. Although progression-free survival (PFS) demonstrated a favorable trend in the overall study population, it did not reach statistical significance. Importantly, Sone-Ve maintained a well-tolerated safety profile, with no new safety concerns identified throughout the study. Clinical investigators noted that metastatic gastric cancer remains one of the most aggressive malignancies with limited treatment options after first-line therapy, making the survival benefit demonstrated by Sone-Ve particularly meaningful for patients facing poor long-term outcomes.
First-in-Class CLDN18.2 ADC Advances Precision Oncology
Sonesitatug vedotin is a potential first-in-class CLDN18.2-targeting antibody-drug conjugate (ADC) that combines a monoclonal antibody targeting CLDN18.2 with a monomethyl auristatin E (MMAE) payload through a protease-degradable linker, enabling selective delivery of cytotoxic therapy to cancer cells. CLDN18.2 has emerged as one of the most promising molecular targets in gastrointestinal oncology, with approximately 60% of advanced gastric and GEJ cancers expressing the biomarker at clinically relevant levels. Each year, an estimated 183,500 patients across the United States, Europe, China, and Japan receive second-line or later treatment for advanced CLDN18.2-positive, HER2-negative gastric and GEJ cancers, highlighting the significant unmet medical need addressed by this therapy. The encouraging Phase III findings further strengthen AstraZeneca’s extensive gastrointestinal oncology pipeline while supporting the broader development of Sone-Ve across additional tumor types and combination treatment strategies.
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AstraZeneca Strengthens Global GI Cancer Innovation Pipeline
The positive Phase III outcome represents a major milestone for AstraZeneca’s expanding gastrointestinal cancer portfolio and reinforces the company’s strategy of advancing precision medicine through targeted biologics and innovative antibody-drug conjugates. Beyond CLARITY-Gastric01, Sone-Ve is currently being evaluated in the Phase III CLARITY-Gastric02 trial as a first-line treatment in combination regimens and is also under investigation in Phase II studies involving pancreatic cancer, biliary tract cancer, and other advanced solid tumors. The therapy has already received Orphan Drug Designation from both the U.S. Food and Drug Administration and the European Commission, along with Breakthrough Designation in China, highlighting its global regulatory momentum. As AstraZeneca continues expanding its oncology pipeline, the success of Sone-Ve underscores the growing impact of ADC technology, biomarker-driven therapies, and precision oncology in improving survival outcomes for patients with advanced gastrointestinal cancers worldwide.
Source: AstraZeneca press release
