November 4th, 2026
Summary by Mark L. Fuerst
The antibody–drug conjugate (ADC) sonesitatug vedotin (Sone-Ve) improved overall survival (OS) compared with standard therapy in patients with previously treated advanced CLDN18.2-positive gastric or gastroesophageal cancer. This is the first time a CLDN18.2-targeting ADC has shown an OS benefit in a phase III trial in this disease.
In the global phase III CLARITY-Gastric 01 trial (Abstract LBA7), after a median follow-up of 8.6 months, in the third- or later-line setting median OS was 10 months in the Sone-Ve group versus 5 months in the investigator-choice group, a 53% reduction in risk of death. Survival also improved in second-line or later treatment, with median OS of 10.6 months versus 6.4 months, a 42% reduction in risk of death. The OS benefit was maintained across CLDN18.2 expression subgroups.
“Sone-Ve is a potential new standard of care in the second-line and higher setting for patients with advanced or metastatic CLDN18.2-positive gastroesophageal carcinoma,” said lead author Rui-Hua Xu MD, PhD, Professor in the Department of Medical Oncology at Sun Yat-sen University Cancer Center in Guangzhou, China, at a press briefing during the ESMO Congress 2026 in Madrid, Spain.
Treatment options remain limited for advanced gastroesophageal cancer patients whose disease progresses after earlier therapies. CLDN18.2 has emerged as a validated therapeutic target following results with the first-line antibody zolbetuximab, Xu said. Sone-Ve is a first-in-class CLDN18.2-targeted ADC that delivers a cell-killing drug directly to tumor cells.
Study Details
In the randomized, open-label trial, 532 patients with previously treated advanced CLDN18.2-positive disease were randomly assigned to Sone-Ve (267 patients) or their investigator’s choice of standard therapy (265 patients). Of these, 355 had received third-line or later treatment. Patients had received 1 or more prior therapies for gastroesophageal cancer expressing CLDN18.2 in 25% or more tumor cells with membranous staining at any intensity.
Patients were initially randomized to Sone-Ve 1.8 mg/kg, Sone-Ve 2.2 mg/kg or investigator’s choice therapy. Post-dose selection, patients were randomized to Sone-Ve 2.2 mg/kg or ramucirumab plus paclitaxel, paclitaxel, or docetaxel in the second-line setting, or irinotecan, trifluridine/tipiracil, or apatinib (China only) in the third-line setting. Randomization was stratified by region, prior gastrectomy, and line of therapy.
The patients’ median age was 57 years, and 61% in the Sone-Ve arm and 55.8% in the investigator’s choice arm had peritoneal metastases, which is associated with poor prognosis, Xu noted. Few patients (less than 4%) had received prior zolbetuximab.
Key Findings
The survival benefit across different levels of CLDN18.2 expression was seen in patients with both high (75% or more tumor cells) and lower (25% to less than 75%) expression levels.
In the second-line and later-line setting, median PFS did not meet the prespecified threshold for statistical significance with Sone-Ve compared with investigator’s choice of therapy (4.2 months versus 3.8 months). “The PFS signal was also favorable with Sone-Ve,” said Xu. Median OS was significantly improved (10.6 months versus 6.4 months) in the intention-to-treat analysis, but subgroup analyses indicated that this may have been due to later-line effects, rather than second-line benefits.
There were fewer severe treatment-related adverse events (TRAE) with Sone-Ve. Grade 3 or higher TRAE occurred in 36% of patients receiving Sone-Ve versus 45% with standard therapy. Hematological side effects were also less common with Sone-Ve (8% versus 16%). However, gastrointestinal side effects were more common with Sone-Ve (11% versus 6%), which Xu said were manageable.
Adverse events led to dose delay or reduction of 36.4% and 21.1% of Sone-Ve patients compared to 40.5% and 23% in the investigator’s choice arm. In the Sone-Ve arm, adverse events resulted in treatment discontinuation for 5% of patients versus 4.4% in the investigator’s choice arm.
ESMO discussant Professor Salah-Eddin Al-Batran from Krankenhaus Nordwest in the University Cancer Center Frankfurt and the Frankfurt Institute of Clinical Cancer Research, Germany, commented, “The CLARITY-Gastric 01 findings are very promising, at least in patients who have had three or more lines of therapy. Despite the rather complicated nature of dual primary endpoints in different settings in the trial, Sone-Ve could become an important new treatment option in the third- and later-line settings based on the doubling of median OS from 5 to 10 months. The situation in the second-line setting is less certain given the lack of a significant difference in PFS, but the safety profile is manageable.”
To what extent Sone-Ve will be active in patients who have already received zolbetuximab in the first-line setting is still unknown. Al-Batran noted that the place of Sone-Ve in the treatment of advanced gastric/gastroesophageal junction cancer will be further established when results are available from the ongoing CLARITY-Gastric 02 phase III trial evaluating Sone-Ve with capecitabine, with or without rilvegostomig, a TIGIT and PD-1 bispecific antibody, as first-line treatment.