Two new ADCs show major survival gains in CLDN18.2-positive gastric cancer

Two CLDN18.2-targeted antibody-drug conjugates (ADCs) delivered striking phase 3 survival data at the 2026 ESMO Congress, potentially reshaping treatment for previously treated advanced gastric and gastroesophageal junction (GEJ) cancers — a space with historically poor outcomes.

Sonesitatug vedotin (AZD0901) met one of its dual primary endpoints in the CLARITY-Gastric01 trial, more than doubling median overall survival (OS) vs investigator's choice chemotherapy in the third-or-later-line setting (10.0 vs 5.0 months). In the broader second-or-later-line population, median OS was 10.6 vs 6.4 months. The OS benefit held across both high and lower CLDN18.2 expression levels, supporting a 25% expression threshold for eligibility. The drug's principal investigator called it "a potential new standard of care" in this setting.

Arcotatug tavatecan (IBI343/TAK-921) also hit both primary endpoints in the G-HOPE-001 trial, improving PFS (5.5 vs 2.9 months) and OS (10.2 vs 6.9 months) vs physician's choice in third-line CLDN18.2-positive, HER2-negative gastric/GEJ adenocarcinoma. Regulatory filings are planned in Japan, and China's NMPA has accepted a priority review application.

By the Numbers:

• Sonesitatug vedotin: 53% reduction in death risk (HR 0.47) in 3rd-line+; 42% reduction (HR 0.58) in 2nd-line+
• Arcotatug tavatecan: 43% reduction in death risk (HR 0.57); objective response rate of 37.4% vs 7.7% with chemotherapy
• Grade 3+ neutropenia was lower with sonesitatug vedotin (10.3%) vs chemotherapy (25.4%), though GI side effects such as nausea were more common (54.4% vs 26.6%)

Why it matters: CLDN18.2-positive gastric/GEJ cancer has limited later-line options. These two ADCs, with distinct mechanisms and payloads, both demonstrate meaningful OS benefits — offering oncologists potentially two new targeted tools for a patient population with few effective therapies.