Wilmington, Del. — AstraZeneca said its experimental antibody-drug conjugate sonesitatug vedotin significantly improved overall survival in patients with previously treated CLDN18.2-positive advanced gastric and gastroesophageal junction cancers in a Phase III trial.
High-level results from the global CLARITY-Gastric01 study showed that sonesitatug vedotin, also known as Sone-Ve, produced a statistically significant and clinically meaningful improvement in overall survival compared with an investigator-selected treatment.
The trial enrolled patients with locally advanced or metastatic gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma whose tumors expressed CLDN18.2 on at least 25% of tumor cells at any staining intensity.
The study met one of its dual primary endpoints by improving overall survival among patients receiving third-line or later treatment. It also met a key secondary endpoint by improving overall survival in the broader population of patients treated in the second-line or later setting.
The trial’s other primary endpoint, progression-free survival as assessed by blinded independent central review, showed a trend favoring Sone-Ve but did not reach statistical significance.
AstraZeneca said the findings could broaden the population considered eligible for CLDN18.2-targeted treatment by using a threshold of at least 25% tumor-cell expression. The company estimates that approximately 60% of gastric and gastroesophageal junction cancers meet that threshold.
“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 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,” said Rui-Hua Xu, M.D., Ph.D., Professor in the Department of Medical Oncology at Sun Yat-Sen University Cancer Center and principal investigator of the trial.
Susan Galbraith, Executive Vice President of Oncology Haematology R&D at AstraZeneca, said the drug could potentially replace conventional chemotherapy for some patients.
“Sone-Ve has the potential to reshape the treatment of gastric cancer by replacing classic chemotherapy with this novel targeted antibody drug conjugate to improve outcomes for patients. These transformative results from the first Phase III 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.
The treatment was generally well tolerated, with no new safety signals identified, according to the company. Its safety profile was consistent with findings from previous studies.
Sone-Ve is designed to target CLDN18.2, a protein expressed in the stomach lining and certain gastrointestinal cancers. The antibody-drug conjugate combines an anti-CLDN18.2 monoclonal antibody with a protease-cleavable linker and the chemotherapy payload monomethyl auristatin E.
CLARITY-Gastric01 is a randomized, open-label, sponsor-blinded study being conducted at 175 centers in 19 countries. Patients were assigned to receive Sone-Ve at one of two doses or an investigator-selected treatment. The 2.2 milligrams-per-kilogram dose administered every three weeks was selected for the Phase III portion.
The company plans to present the results at an upcoming medical meeting and submit the findings to regulatory authorities.
Sone-Ve has received Orphan Drug Designation from the U.S. Food and Drug Administration and the European Commission for gastric and gastroesophageal junction cancers. It has also received Breakthrough Therapy Designation in China for second-line gastric cancer.
AstraZeneca acquired global rights to develop and commercialize Sone-Ve through an exclusive licensing agreement with KYM Biosciences in 2023.
The drug is also being evaluated in the Phase III CLARITY-Gastric02 trial as a first-line treatment in combination with capecitabine, with or without rilvegostomig. Additional Phase II studies are examining the therapy in pancreatic, biliary tract and other solid tumors.
