First CLDN18.2 ADC (Sonesitatug Vedotin, CLARITY-Gastric01) in Advanced Gastric Cancer: AstraZeneca (Industry Update) | July 2026

Introduction:

Claudin 18.2 (CLDN18.2) has emerged as a key therapeutic target in gastric and gastroesophageal junction (GEJ) adenocarcinoma. The Phase III CLARITY-Gastric01 trial evaluated sonesitatug vedotin, an anti-CLDN18.2 antibody-drug conjugate (ADC), in previously treated CLDN18.2-positive advanced gastric/GEJ cancer.

Why was this study needed?

• Patients progressing after first-line therapy have limited treatment options and poor survival.
• Approximately 60% of gastric/GEJ cancers express CLDN18.2 (≥25%), making it an attractive therapeutic target.
• No CLDN18.2-targeted ADC had previously demonstrated an overall survival benefit in Phase III trials.
• More effective therapies are needed beyond chemotherapy and immune checkpoint inhibitors.
• ADCs offer targeted drug delivery with the potential to improve efficacy while limiting systemic toxicity.

Results:

• Sonesitatug vedotin met its dual primary endpoint, demonstrating a significant improvement in overall survival in patients with third-line or later CLDN18.2-positive advanced gastric/GEJ cancer.
• The trial also achieved a key secondary endpoint, showing an overall survival benefit across the broader second-line and later treatment population.
• Although progression-free survival showed a favorable trend in the second-line setting, it did not reach statistical significance.

Clinical Impact:

This represents the first Phase III evidence of an overall survival benefit for a CLDN18.2-targeted antibody-drug conjugate in advanced gastric cancer. If confirmed in the full peer-reviewed publication and approved by regulatory authorities, sonesitatug vedotin could become an important treatment option for patients with CLDN18.2-positive gastric/GEJ adenocarcinoma after prior systemic therapy.

Bottom Line:

The Phase III CLARITY-Gastric01 trial marks a major advance in biomarker-driven gastric cancer therapy. Sonesitatug vedotin is the first anti-CLDN18.2 ADC to demonstrate an overall survival benefit, establishing CLDN18.2-targeted ADC therapy as a promising new option for previously treated advanced gastric and GEJ cancers.