Positive results from the CLARITY-Gastric01 global phase 3 trial showed AstraZeneca’s sonesitatug vedotin (Sone-Ve) demonstrated a statistically significant and highly clinically meaningful improvement in Overall Survival (OS) in 2nd- and later-line Claudin 18.2-positive advanced gastric cancers versus investigator’s choice of therapy.

The trial included patients with locally advanced or metastatic gastric cancer, gastroesophageal junction (GEJ) cancer, or esophageal adenocarcinoma (EAC) with Claudin 18.2 (CLDN18.2) expression on at least 25 percent of tumor cells at any staining intensity, expanding the patient population beyond the current definition of CLDN18.2 positivity.

The trial had dual primary endpoints of OS in the 3rd- and later-line treatment setting and Progression-Free Survival (PFS) in the overall trial population of patients treated in the 2nd- and later-line setting. OS in the overall trial population was a key secondary endpoint.

In a planned interim analysis, Sone-Ve reduced the risk of death by 42 percent compared to investigator’s choice of therapy (based on an OS hazard ratio [HR] of 0.58; 95 percent Confidence Interval [CI] 0.47–0.73; p<0.000004) in the overall trial population. Median OS was 10.6 months for patients treated with Sone-Ve compared to 6.4 months for investigator’s choice of therapy.

In the 3rd- and later-line setting, Sone-Ve reduced the risk of death by 53 percent compared to investigator’s choice of therapy (OS HR of 0.47; 95 percent CI 0.36-0.62; p<0.000001). Median OS doubled for patients treated with Sone-Ve (10.0 versus 5.0 months). The OS benefit observed was consistent across most predefined subgroups in both the overall trial population and the 3rd- and later-line setting, including subgroups based on CLDN18.2 expression levels (≥25 percent-<75 percent and ≥75 percent).

Rui-Hua Xu, MD, PhD, Professor, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China, and principal investigator of the trial said, “These are remarkable survival results for Sone-Ve in 2nd- and later-line metastatic gastric cancer, a disease where patients face a poor prognosis once initial therapy fails. As the first CLDN18.2-targeted therapy to show survival benefit in this setting, extending median survival by more than 4 months compared to investigator's choice of therapy, Sone-Ve could transform the treatment paradigm for patients with CLDN18.2 expression.”

For the other dual primary endpoint of PFS as assessed by Blinded Independent Central Review (BICR) in the overall trial population, results showed a trend toward improved PFS in patients treated in the 2nd- and later-line setting but did not reach statistical significance. An exploratory analysis of investigator-assessed PFS showed a more pronounced treatment effect (PFS HR 0.59; 95 percent CI 0.48-0.73) that was consistent with observed OS results in this setting.

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said, “Sone-Ve has set a new benchmark for survival in 2nd- and later-line metastatic gastric cancer, and these data support expanding this precision treatment to a much broader population of patients with Claudin 18.2 expression. Sone-Ve could replace traditional chemotherapy-based regimens as a new Standard of Care in this setting, and these unprecedented data reinforce our confidence in its potential across CLDN18.2-positive cancers."