AstraZeneca’s sonesitatug vedotin, known as Sone-Ve, cut the risk of death by 42 percent against investigator’s choice of therapy in patients with CLDN18.2-positive advanced gastric or gastroesophageal junction cancer treated in the second line or later, in the global Phase 3 CLARITY-Gastric01 trial presented at ESMO on October 25. Median overall survival was 10.6 months on Sone-Ve (267 patients) against 6.4 months (265 patients), a hazard ratio of 0.58 (95 percent confidence interval 0.47 to 0.73). In the third-line and later population, which carried one of the trial’s dual primary endpoints, the effect was larger: a 53 percent reduction in the risk of death (hazard ratio 0.47), with median survival of 10.0 months against 5.0 months. The trial enrolled tumours with CLDN18.2 expression on at least 25 percent of cells, a broader definition than the one used for existing CLDN18.2 treatments, covering up to about 60 percent of patients in this setting, and the survival benefit was consistent across expression levels.
The qualification sits in the same results table. Progression-free survival by blinded independent central review, the other dual primary endpoint in the overall population, was 4.2 months against 3.8 months (hazard ratio 0.77) with a p value of 0.053, which does not reach statistical significance, although progression assessed by investigators favoured Sone-Ve more clearly (hazard ratio 0.59). Reuters reported the same tension from Madrid: a survival gain larger than analysts expected, analysts had looked for a hazard ratio of about 0.7 or lower with at least two months of gain, alongside the missed progression endpoint.
Sone-Ve matters to AstraZeneca beyond one indication. It is the company’s first fully owned antibody-drug conjugate to reach Phase 3 survival data, licensed from China’s KYM Biosciences in 2023, after a decade in which its ADC business was built through the Daiichi Sankyo partnership behind Enhertu and Datroway. The company says two more owned ADCs are in late-stage trials and that it plans to file Sone-Ve for approval.
The commercial forecasts diverge sharply, and readers should hold both. AstraZeneca has guided to peak sales of 3 billion to 5 billion dollars for Sone-Ve, Reuters reported, while analyst estimates are closer to 1 billion dollars. Which figure is closer will depend on the label regulators grant on a survival win with a formally missed progression endpoint, and on how much of the broader CLDN18.2 population the label covers.