A TARGETED therapy reduced the hazard of death by 53% compared with investigator-selected treatment in patients receiving third-line or later therapy for a specific type of advanced carcinoma, according to Phase III results presented at the European Society for Medical Oncology (ESMO) Congress 2026.
In the CLARITY-Gastric 01 trial, median overall survival in patients with CLDN18.2-positive gastroesophageal cancer reached 10.0 months with sonesitatug vedotin, compared with 5.0 months with the comparator. A significant survival benefit was also seen across the broader second-line-or-later population.
The findings support sonesitatug vedotin as a potential treatment option after previous therapy, although the trial did not meet its progression-free survival significance threshold.
Sonesitatug vedotin is an antibody–drug conjugate targeting Claudin 18.2 (CLDN18.2), The antibody-drug conjugate delivers monomethyl auristatin E, a drug that disrupts cancer cell division.
The global, open-label trial enrolled patients with unresectable, locally advanced or metastatic gastroesophageal carcinoma after at least one previous therapy. Tumours required membranous CLDN18.2 staining of any intensity in at least 25% of cells.
The reported comparison included 267 patients assigned to sonesitatug vedotin 2.2 mg/kg and 265 to investigator-selected therapy. Comparator options included ramucirumab plus paclitaxel, taxane chemotherapy and later-line treatments, depending on previous treatment line.
The dual primary endpoints were overall survival in the third-line-or-later population and progression-free survival by blinded independent central review in the full population. Overall survival in the full population was a key secondary endpoint.
At the data cut-off of 31 May 2026, median follow-up was 8.6 months.
Among patients receiving third-line or later treatment, median overall survival was 10.0 months with sonesitatug vedotin versus 5.0 months with investigator-selected treatment. This corresponded to a 53% reduction in the risk of death during follow-up (HR: 0.47; 95% CI: 0.36–0.62; p<0.001).
Across the broader second-line-or-later population, median overall survival was 10.6 versus 6.4 months, corresponding to a 42% reduction in the risk of death (HR: 0.58; 95% CI: 0.47–0.73; p<0.001).
Median progression-free survival was 4.2 versus 3.8 months. Although the hazard ratio suggested a 23% reduction in the risk of disease progression or death (HR: 0.77; 95% CI: 0.62–0.96), the reported p value of 0.05 did not meet the trial’s significance threshold for this endpoint.
Grade 3 or higher treatment-related adverse events occurred in 36.4% with sonesitatug vedotin and 44.8% with comparator treatment. Severe gastrointestinal toxicity occurred in 11.1% versus 6.3%, while severe haematological toxicity occurred in 7.7% versus 15.9%.
Treatment-related adverse events led to discontinuation in 3.1% and 4.4%, respectively. Treatment-related deaths occurred in three ADC recipients and two comparator recipients.
The investigators concluded that the overall survival benefit supports sonesitatug vedotin as a potential second-line-or-later option for advanced CLDN18.2-positive disease, with its place in treatment sequencing requiring further assessment.
IARC estimates indicate over 980,000 new stomach cancer cases worldwide in 2024. Although this figure covers stomach cancer overall, rather than the specific biomarker-defined trial population, the results of the CLARITY trial show promise for the use of antibody- drug conjugate target therapies to treat advanced gastric cancer.
Reference
Xu R-H et al. CLARITY-Gastric 01: a phase 3 study of sonesitatug vedotin in second or later-line advanced or metastatic Claudin 18.2-positive gastroesophageal carcinoma. Abstract LBA7. NCT06346392. Abstract. ESMO Congress, 23-27 October 2026.
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