Sonesitatug Vedotin Extends Survival in Advanced Gastric Cancer

Patients with CLDN18.2-positive gastric cancer who had tried other treatments lived significantly longer on sonesitatug vedotin according to results from the phase 3 CLARITY-Gastric01 trial.

Sonesitatug vedotin is an antibody-drug conjugate (ADC) that targets the CLDN18.2 protein expressed on certain gastric cancer cells. The antibody delivers a cytotoxic chemotherapy payload to CLDN18.2-expressing cells, although some exposure to normal tissues can still occur.

The international study tested the drug in patients whose tumors carry Claudin 18.2 (CLDN18.2), a protein found on the surface of many stomach cancer cells. The trial included people with:

• advanced or metastatic stomach cancer
• GEJ cancer, a related cancer where the esophagus meets the stomach
• esophageal adenocarcinoma, a type of esophageal cancer

All participants had gone through at least one round of treatment that had stopped working.

"Metastatic gastric cancer is an aggressive disease with very limited options once patients progress after first-line treatment," Dr. Rui-Hua Xu, principal investigator of the trial, said in a press release issued by AstraZeneca. "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."

Advanced gastric cancer remains difficult to treat, particularly after first-line therapy fails, with limited treatment options available.

What did the CLARITY-Gastric01 trial find?

The survival benefit held across two groups: patients who had tried at least two prior treatments, and a broader group who had tried at least one.

Investigators reported that the overall survival benefit was observed across prespecified subgroups, including patients with varying levels of CLDN18.2 expression. Detailed subgroup analyses have not yet been released.

Susan Galbraith, executive vice president of oncology research and development at AstraZeneca, said in the press release “the findings suggest the drug could provide a targeted alternative to conventional chemotherapy for some patients.”

How was the CLARITY-Gastric01 trial designed?

The study took place at 175 hospitals in 19 countries across North America, Europe, South America and Asia. Everyone enrolled had a tumor that tested positive for CLDN18.2 on at least 25% of cancer cells.

The trial ran in two stages. In the first stage, patients were randomly split into three groups. One received a higher dose of sonesitatug vedotin (2.2 mg/kg) every three weeks, another received a lower dose (1.8 mg/kg) on the same schedule, and the third received the treatment their doctor thought was best. Once researchers determined the 2.2 mg/kg as the preferred dose, patients enrolling in the trial's second stage received that dose.

Researchers also used results from the trial to evaluate a lab test called the Ventana SP455 assay, designed to identify which patients have enough CLDN18.2 in their tumors to benefit from this kind of treatment.

What side effects did patients experience?

According to AstraZeneca, the safety profile was consistent with earlier studies, and no new safety concerns were identified.

The drug has received orphan drug designation from the U.S. Food and Drug Administration and the European Commission and breakthrough therapy designation in China for certain patients with advanced gastric cancer.

Full results from the trial will be presented at an upcoming medical conference and submitted to health regulators around the world.

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.

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