Promising results from a major international clinical trial have highlighted a new targeted treatment, sonesitatug vedotin (Sone‑Ve), for people with advanced stomach (gastric) and gastroesophageal junction (GEJ) cancers whose tumors carry a marker called Claudin 18.2 (CLDN18.2).
What the study found
- The CLARITY‑Gastric01 Phase III trial showed that Sone‑Ve helped patients live significantly longer than those receiving standard chemotherapy chosen by their doctor, when used in the second‑line (after first treatment has stopped working) and later‑line settings.
- This is the first Phase III study to show a survival benefit with an anti‑CLDN18.2 antibody‑drug conjugate (ADC) in advanced gastric or GEJ cancer, marking an important step forward for this group of patients who currently have few effective options.
- The study included people with locally advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma whose tumors expressed CLDN18.2 in at least 25% of cancer cells. Based on these results, this 25% threshold may be used to define CLDN18.2‑positive disease, potentially expanding eligibility to about 60% of patients in this setting.
Survival and disease control
- The trial’s main goal was to see whether Sone‑Ve could improve overall survival (how long patients live) in those receiving it as third‑line or later treatment. This goal was met, with a statistically significant and clinically meaningful survival benefit compared with standard treatment.
- A key secondary goal was to look at overall survival in all patients treated in the second‑line and later‑line setting. Here too, Sone‑Ve showed a significant and meaningful improvement.
- For progression‑free survival (how long the cancer stays controlled without worsening), there was a favorable trend with Sone‑Ve in the overall group, but this measure did not reach statistical significance.
Why this matters for patients
- Most people with gastric or GEJ cancers are diagnosed when the disease is already advanced or has spread, and many will see their cancer progress after first‑line chemotherapy or targeted therapy. At that stage, treatment options are limited and fewer than 1 in 5 patients are alive one year later.
- CLDN18.2 has emerged as an important new target in these cancers. Around 60% of gastric and GEJ tumors show CLDN18.2 in 25% or more of their cancer cells, meaning a majority of patients could potentially benefit from a CLDN18.2‑targeted treatment if approved.
- Each year, roughly 183,500 patients in the US, EU, China and Japan are treated in the second‑line and later‑line setting for advanced or metastatic CLDN18.2‑positive, non‑HER2‑positive gastric/GEJ cancers—representing a large group with high unmet need.
What is Sone‑Ve?
Sone‑Ve is a type of targeted cancer medicine called an antibody‑drug conjugate (ADC). It is designed to recognize and bind to CLDN18.2 on cancer cells and then deliver a powerful chemotherapy drug (MMAE) directly into those cells, aiming to limit damage to healthy tissue.
In CLARITY‑Gastric01, Sone‑Ve was generally well tolerated, with a safety profile consistent with what doctors have seen in earlier studies and no new safety concerns identified.
Expert perspectives
Investigators highlighted that metastatic gastric cancer is an aggressive disease with very limited options once first‑line therapy fails, and that Sone‑Ve is the first CLDN18.2‑targeted ADC to show an overall survival benefit in this setting. They noted its potential to become a new precision treatment for a broader group of patients whose tumors express CLDN18.2.
Oncology leaders have noted that Sone‑Ve could help “reshape” treatment by offering a targeted alternative to traditional chemotherapy, and emphasized that this is the first pivotal Phase III readout from this wholly owned ADC portfolio.
Next steps
Detailed trial results will be presented at an upcoming medical conference and shared with health authorities around the world to support potential regulatory submissions.
Sone‑Ve already holds Orphan Drug Designation for gastric and GEJ cancers in the US and EU, and Breakthrough Designation in China for second‑line gastric cancer, reflecting recognition of its potential in a serious, hard‑to‑treat disease.
Additional studies are ongoing, including a Phase III trial of Sone‑Ve in combination with other medicines in the first‑line setting for gastric, GEJ and esophageal adenocarcinoma, as well as Phase II trials in other CLDN18.2‑positive cancers such as pancreatic and biliary tract tumors.
If you or a loved one has advanced gastric or GEJ cancer, these findings will not change treatment immediately but signal that new, more personalized options may be on the horizon. Patients should talk with their oncology team about current standard treatments, clinical trial opportunities, and whether CLDN18.2 testing is appropriate for their tumor.
References
- Poniewierska-Baran A, et al. Claudin18.2 as a Promising Therapeutic Target in Gastric Cancer. Cells. 2025;14(16):1285.
- https://www.astrazeneca.com/media-centre/press-releases/2026/sone-ve-improved-survival-in-gastric-cancers.html
