AstraZeneca reports an overall-survival benefit with sonesitatug vedotin in advanced CLDN18.2-positive gastric cancer, while the primary PFS endpoint missed statistical significance.
Written By: Malavatu Satvika, PharmD
Reviewed By: Pharmacally Editorial Team
AstraZeneca reported positive Phase III results for sonesitatug vedotin (Sone-Ve), an investigational antibody-drug conjugate (ADC), in previously treated advanced or metastatic gastric, gastroesophageal junction (GEJ), or oesophageal adenocarcinoma expressing Claudin 18.2 (CLDN18.2). In CLARITY-Gastric01, Sone-Ve improved overall survival (OS) compared with investigator’s choice of therapy. However, the blinded independent central review (BICR)-assessed progression-free survival (PFS) endpoint did not reach statistical significance.
CLARITY-Gastric01: Trial Design
CLARITY-Gastric01 was a global, randomised, open-label, sponsor-blinded Phase III trial conducted across 175 centres in 19 countries. Eligible patients had locally advanced or metastatic gastric, GEJ or oesophageal adenocarcinoma, with CLDN18.2 membranous staining at any intensity in at least 25% of tumour cells.
During Stage 1, patients were randomised to Sone-Ve at 2.2 mg/kg or 1.8 mg/kg every three weeks, or investigator’s choice of therapy. Stage 2 continued with 2.2 mg/kg every three weeks as the recommended Phase III dose. The reported efficacy results reflect the selected 2.2 mg/kg regimen.
The dual primary endpoints were OS in the third-line-and-later (3L+) population and BICR-assessed PFS in the overall second-line-and-later (2L+) population. OS in the overall population was a key secondary endpoint. The data cutoff was 31 May 2026.
Overall-Survival Findings
In a planned interim analysis, Sone-Ve reduced the relative hazard of death by 42% in the overall 2L+ population. Median OS was 10.6 months versus 6.4 months with investigator’s choice (hazard ratio [HR] 0.58; 95% confidence interval [CI] 0.47–0.73; p<0.000004). The analysis included 267 patients receiving Sone-Ve and 265 receiving comparator treatment.
The primary OS endpoint was also met in the 3L+ population. Median OS was 10.0 months versus 5.0 months, respectively (HR 0.47; 95% CI 0.36–0.62; p<0.000001), representing a 53% lower relative hazard of death. This analysis included 178 patients receiving Sone-Ve and 177 receiving investigator’s choice.
At 12 months, OS rates were 42.6% versus 27.8% in the overall population and 38.1% versus 18.1% in the 3L+ population, respectively.
The OS benefit extended across the reported CLDN18.2 expression subgroups in the overall population. The HR was 0.59 (95% CI 0.45–0.78) for expression of at least 75% and 0.63 (95% CI 0.42–0.94) for expression of at least 25% but below 75%. These findings suggest that the observed benefit was not restricted to tumours with high CLDN18.2 expression, although they do not establish equivalent treatment effects across subgroups.
PFS and Safety Findings
BICR-assessed median PFS was 4.2 months with Sone-Ve versus 3.8 months with investigator’s choice (HR 0.77; 95% CI 0.62–0.96; reported p=0.053193). AstraZeneca reported that this primary endpoint did not reach statistical significance.
An exploratory investigator-assessed analysis showed median PFS of 4.4 months versus 3.0 months (HR 0.59; 95% CI 0.48–0.73). This finding is supportive but does not replace the prespecified BICR assessment.
Grade 3 or higher treatment-related adverse events occurred in 36.4% of patients receiving Sone-Ve compared with 44.8% receiving investigator’s choice. AstraZeneca reported a manageable tolerability profile and no new safety signals.
Clinical Interpretation
CLARITY-Gastric01 is the first Phase III trial reported to demonstrate a statistically significant and clinically meaningful OS benefit with a CLDN18.2-targeted ADC in this treatment setting. The findings are relevant because they show a survival benefit in both the 3L+ primary analysis population and the broader 2L+ population, including patients with lower levels of CLDN18.2 expression within the study’s eligibility criteria.
The PFS result nevertheless requires separate consideration. The BICR-assessed endpoint did not meet statistical significance, despite a hazard ratio favouring Sone-Ve, while investigator-assessed PFS was exploratory. The available results do not establish why the OS and PFS findings differed.
Sone-Ve remains investigational. Further evaluation of the complete clinical dataset, safety profile and regulatory requirements will be needed to determine its potential role in treatment.
Reference
Sonesitatug vedotin reduced the risk of death by 42% in 2nd- and later-line CLDN18.2-positive advanced gastric/GEJ cancers in CLARITY-Gastric01, AstraZeneca, 25 October 2026
AZD0901 Compared with Investigator’s Choice of Therapy in Participants with Second- or Later-line Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Claudin18.2, ClinicalTrials.gov ID NCT06346392
About the Writer
Malavatu Satvika (Linkedin) is a Pharm.D professional and aspiring healthcare medical writer with clinical exposure and research experience. Her interests include medical writing, drug safety, pharmaceutical research, and evidence-based healthcare communication. She has contributed to two research publications in pharmaceutical journals and has gained practical experience in prescription review, patient counselling, medication review, adverse drug reaction monitoring, drug information services, literature review, and clinical documentation through regular hospital training.
She has completed certifications in clinical research, ICH-GCP E6(R3), data management for clinical research, and congenital hypothyroidism. With a strong foundation in pharmacy, clinical practice, and scientific research, she aims to translate complex medical and pharmaceutical information into accurate, clear, and evidence-based healthcare content. She is also preparing to pursue a PhD and further develop her expertise in medical writing and pharmaceutical research.