Sonesitatug Vedotin Improves Survival in CLDN18.2-Positive Gastric Cancer

Sonesitatug vedotin (Sone-Ve), a first-in-class anti-CLDN18.2 antibody-drug conjugate (ADC), demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared with investigator's choice of chemotherapy in patients with second-line and later CLDN18.2-positive advanced gastric and gastroesophageal junction (GEJ) cancers.¹

Positive high-level results from the global CLARITY-Gastric01 phase 3 trial (NCT06346392) showed that Sone-Ve met its dual primary end point of OS in the third-line and later-line treatment setting and its key secondary end point of OS in the overall trial population of patients treated in the second-line and later setting. The magnitude of OS improvement was described as statistically significant and highly clinically meaningful.

For the trial's other dual primary end point of progression-free survival (PFS) as assessed by blinded independent central review in the second-line and later-line setting, results showed a trend toward improvement that did not reach statistical significance. Full data will be presented at a forthcoming medical meeting and shared with global regulatory authorities, according to AstraZeneca, the developer of the ADC.

"Metastatic gastric cancer is an aggressive disease with very limited options once patients progress after first-line treatment," Rui-Hua Xu, MD, PhD, Professor in the Department of Medical Oncology at Sun Yat-Sen University Cancer Center in Guangzhou, China, and principal investigator of the trial, stated in a news release.¹ "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."

The CLARITY-Gastric01 findings are supported by earlier-phase clinical data. In the global phase 2 CLARITY-PanTumor01 study (NCT06219941), presented at the 2026 American Society of Clinical Oncology Annual Meeting, Sone-Ve monotherapy at 2.2 mg/kg intravenously every 3 weeks produced a confirmed objective response rate of approximately 30% and showed a manageable safety profile in patients with CLDN18.2-positive advanced or metastatic gastric and GEJ cancers who had received 1 to 2 prior lines of systemic therapy, building on earlier first-in-human data from a Chinese phase 1 study (KYM901) in which the agent demonstrated initial evidence of activity in this setting.^2,3

Safety of Sone-Ve

The safety profile of Sone-Ve in CLARITY-Gastric01 was consistent with the established profile of the agent, with no new safety signals identified.¹ The known safety profile of Sone-Ve is principally characterized by adverse events consistent with its MMAE payload and anti-CLDN18.2 mechanism, with myelosuppression, gastrointestinal effects, and peripheral neuropathy among the expected effects of the class.

CLARITY-Gastric01 Design and Patient Population

CLARITY-Gastric01 is a randomized, open-label, sponsor-blinded, multicenter, global phase 3 trial evaluating Sone-Ve as a second-line and later-line therapy in patients with locally advanced or metastatic gastric cancer, GEJ cancer, or esophageal adenocarcinoma (EAC) with CLDN18.2 expression in at least 25% of tumor cells at any immunohistochemistry staining intensity. In Stage 1 of the trial, which served as a dose selection phase, patients were randomized 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. In Stage 2, the trial continued with Sone-Ve 2.2 mg/kg as the recommended phase 3 dose. The trial was conducted at 175 centers across 19 countries, including sites in North America, Europe, South America, and Asia.

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.¹ AstraZeneca is also evaluating Sone-Ve in the phase 3 CLARITY-Gastric02 trial in combination with capecitabine, with or without rilvegostomig, as first-line therapy in advanced or metastatic gastric cancer, GEJ cancer, and EAC.¹

REFERENCES

1. Sonesitatug vedotin demonstrated a statistically significant and highly clinically meaningful improvement in overall survival in 2nd and later-line CLDN18.2-positive advanced gastric/GEJ cancers. News release. AstraZeneca. July 27, 2026. Accessed July 27, 2026. https://tinyurl.com/2uxbuasj

2. Shitara K, Yamaguchi K, Shoji H, et al. Sonesitatug vedotin (Sone-Ve) monotherapy in patients with claudin 18.2-positive advanced or metastatic gastric or gastroesophageal junction cancers: data from CLARITY-PanTumor01. J Clin Oncol. 2026;44(suppl 16):4023. doi:10.1200/JCO.2026.44.16_suppl.4023

3. Shitara K, Xu RH, Xu J, et al. Claudin 18.2-targeting antibody-drug conjugate CMG901 in patients with advanced gastric or gastro-oesophageal junction cancer (KYM901): a multicentre, open-label, single-arm, phase 1 trial. Lancet Oncol. 2024;25(5):660-672. doi:10.1016/S1470-2045(24)00072-X