Sonesitatug Vedotin Improves Overall Survival in CLDN18.2+ Gastric Cancer

Sonesitatug vedotin (Sone-Ve), an antibody-drug conjugate (ADC) targeting Claudin 18.2 (CLDN18.2), significantly improved overall survival (OS) in patients with second- and later-line CLDN18.2-positive advanced gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma cancer compared with investigator’s choice of therapy, according to a news release from AstraZeneca, the agent’s developer.¹

The positive high-level results come from the phase 3 CLARITY-Gastric01 trial (NCT06346392), which the company described as the first phase 3 study to demonstrate an OS benefit with an anti-CLDN18.2 ADC in this treatment setting.

The trial met its dual primary end point of OS in patients treated in the third-line-or-later setting, as well as a key secondary end point of OS in the overall trial population of patients treated in the second-line-or-later setting, of which the results were statistically significant and clinically meaningful. Progression-free survival (PFS), assessed by blinded independent central review as the trial’s other dual primary end point in the second-line-or-later setting, showed a trend toward improvement but did not reach statistical significance. Sone-Ve was reported to be well tolerated, with a safety profile consistent with prior experience and no new safety signals identified.

Full data from CLARITY-Gastric01 are expected to be presented at an upcoming medical meeting and shared with global regulatory authorities.

“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 [OS] benefit in this setting and has the potential to establish a new precision treatment for a broader population of patients with CLDN18.2 expression,” Rui-Hua Xu, MD, PhD, professor in the Department of Medical Oncology at Sun Yat-Sen University Cancer Center, Guangzhou, China, and principal investigator of the trial, said in the press release.¹

CLARITY-Gastric01 is a randomized, open-label, sponsor-blinded, multicenter, global trial enrolling patients with locally advanced or metastatic gastric cancer, GEJ cancer, or esophageal adenocarcinoma expressing CLDN18.2 in at least 25% of tumor cells at any staining intensity by immunohistochemistry.^1,2

The study enrolled 594 patients 18 years and older across 175 centers in 19 countries spanning North America, Europe, South America, and Asia. In the trial’s dose-selection stage, patients were randomly assigned 1:1:1. Of note, patients will continue to be randomly assigned until a 1:1 ratio remains. Patients were given Sone-Ve monotherapy at 2.2 mg/kg or 1.8 mg/kg every 3 weeks, or investigator's choice of therapy as a comparator, which per ClinicalTrials.gov could include ramucirumab (Cyramza) plus paclitaxel, paclitaxel, docetaxel, irinotecan, TAS-102 (Lonsurf), or apatinib (Aitan). The trial’s second stage continued with the 2.2 mg/kg dose as the recommended phase 3 dose.

A related trial design paper presented at the 2026 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium published in the Journal of Clinical Oncology characterized gastric and GEJ cancer as the fifth most diagnosed cancer and fourth leading cause of cancer-related death worldwide, noting the poor prognosis associated with the disease once patients progress beyond first-line therapy.³

Susan Galbraith, executive vice president of Oncology Hematology Research and Development at AstraZeneca, said the results underscore the potential for Sone-Ve to replace classic chemotherapy in this setting. “These transformative results from the first phase 3 readout for Sone-Ve, together with our broad development program, highlight the potential for Sone-Ve to become an important new medicine in CLDN18.2-positive cancers,” Galbraith said.

Sone-Ve, also known as AZD0901, comprises an anti-CLDN18.2 monoclonal antibody linked to a monomethyl auristatin E payload via a protease-degradable linker. The agent has received orphan drug designation from the FDA and the European Commission for gastric and GEJ cancers, along with breakthrough designation in China for second-line treatment of gastric cancer. Beyond CLARITY-Gastric01, Sone-Ve is being evaluated as a first-line treatment in combination with capecitabine, with or without rilvegostomig, in the phase 3 CLARITY-Gastric02 trial, and in earlier-phase studies across additional tumor types.

References

1. Sonesitatug vedotin demonstrated a statistically significant and highly clinically meaningful improvement in overall survival in 2nd and later-line CLDN18.2-positive advanced gastric/GEJ cancers. News release. AstraZeneca. July 27, 2026. Accessed July 27, 2026. https://tinyurl.com/yjvyvvba
2. AZD0901 compared with investigator's choice of therapy in participants with second- or later-line advanced or metastatic gastric or gastroesophageal junction adenocarcinoma expressing Claudin18.2. Updated July 9, 2026. Accessed July 27, 2026. https://tinyurl.com/3prdhcvj
3. Janjigian YY, Elimova E, Zhang J, et al. CLARITY-Gastric 01: a randomized phase 3 study of sonesitatug vedotin (sone ve), a Claudin18.2 (CLDN18.2)-targeted antibody-drug conjugate, in second- or later-line (2L+) advanced gastric or gastroesophageal junction cancer (GC/GEJC). J Clin Oncol. 2026;44(2_suppl):TPS462. doi: 10.1200/JCO.2026.44.2_suppl.TPS462