Treatment with sonesitatug vedotin (Sone-Ve) led to a statistically significant and highly clinically meaningful improvement in overall survival (OS) compared with investigator's choice of therapy in the second- or later-line for patients with Claudin-18.2 (CLDN18.2)–positive advanced or metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma, meeting a dual primary end point of OS in the third- and later-line setting of the phase 3 CLARITY-Gastric01 trial (NCT06346392).1
The trial also met a key secondary end point of OS in the overall trial population of patients treated in the second- and later-line setting, demonstrating a statistically significant and highly clinically meaningful improvement, according to a news release from AstraZeneca.
For the other dual primary end point of progression-free survival (PFS) as assessed by blinded independent central review in patients treated in the second- and later-line setting, results showed a trend toward improvement with Sone-Ve but did not reach statistical significance.
AstraZeneca noted that CLARITY-Gastric01 is the first phase 3 trial to show an OS benefit with an anti-CLDN18.2 antibody-drug conjugate (ADC) in this setting.
Safety data showed that Sone-Ve was well tolerated, with a profile consistent with the known safety profile of the agent, and no new safety signals were identified.
“Metastatic gastric cancer is an aggressive disease with very limited options once patients progress after first-line treatment,” Rui-Hua Xu, MD, PhD, stated in a news release. “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.”
Xu is a professor in the Department of Medical Oncology at Sun Yat-Sen University Cancer Center in Guangzhou, China, and principal investigator of the trial.
was a randomized, open-label, sponsor-blinded, multicenter, global phase 3 trial evaluating Sone-Ve as a second- and later-line therapy for patients with advanced or metastatic gastric cancer, GEJ cancer, or esophageal adenocarcinoma with CLDN18.2 expression on at least 25% of tumor cells at any staining intensity.1,2
The trial enrolled approximately 594 patients across 175 centers in 19 countries, spanning North America, Europe, South America, and Asia.1,2
In dose escalation during stage 1, patients were randomly assigned 1:1:1 to receive Sone-Ve monotherapy at 2.2 mg/kg or 1.8 mg/kg every 3 weeks, or investigator's choice of therapy as the comparator arm.1 In stage 2, the trial continued with Sone-Ve given at 2.2 mg/kg as the recommended phase 3 dose.
The dual primary end points were PFS as assessed by blinded independent central review in the second- and later-line setting and OS in the third- and later-line setting, with a key secondary end point of OS in the second- and later-line setting. Efficacy analyses will also serve to evaluate the clinical performance of the Ventana SP455 assay for identifying patients with advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma expressing CLDN18.2 who may benefit from the agent.
CLDN18.2 has emerged as an important therapeutic target in gastric/GEJ cancers, an estimated 60% of which express the protein in 25% or more of tumor cells; the majority of these patients are diagnosed at an advanced or metastatic stage, where prognosis is poor and treatment options are limited.
The full data from CLARITY-Gastric01 will be presented at a forthcoming medical meeting and shared with global regulatory authorities. Sone-Ve has received orphan drug designation from the FDA and the European Commission for the treatment of gastric and GEJ cancers, and breakthrough designation in China for the second-line treatment of gastric cancer. The agent, a potential first-in-class CLDN18.2-targeting ADC with a monomethyl auristatin E payload, is also under evaluation in the phase 3 CLARITY-Gastric02 trial in the first-line setting and in phase 2 studies across additional CLDN18.2-positive tumor types.1
“Sone-Ve vedotin 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,” Susan Galbraith, executive vice president, Oncology Haematology R&D at AstraZeneca, added in a news release. “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.”
