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Sonesitatug vedotin plus capecitabine, with or without rilvegostomig, for CLDN18.2-positive advanced gastric, gastroesophageal junction, or esophageal adenocarcinoma

A Phase III, Multicentre, Randomised Controlled Study of Sonesitatug Vedotin in Combination With Capecitabine With or Without Rilvegostomig in First-Line Claudin18.2-Positive, HER2-Negative, Advanced/Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma (CLARITY-Gastric 02)

Phase 3 Interventional AstraZeneca · NCT07431281

This trial will test whether adding sonesitatug vedotin to capecitabine, with or without rilvegostomig, helps people with untreated CLDN18.2-positive, HER2-negative advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment2130 (estimated)
Ages18 Years and up
SexAll
SponsorAstraZeneca Industry-sponsored
Locations258 sites (Phoenix, Arizona and 257 other locations)
Trial IDNCT07431281 on ClinicalTrials.gov

What this trial studies

This Phase 3, first-line trial enrolls adults with unresectable or metastatic CLDN18.2-positive, HER2-negative gastric, gastroesophageal junction, or distal esophageal adenocarcinoma. Participants are assigned to one of two cohorts based on PD-L1 status and immune checkpoint inhibitor eligibility: Cohort 1 receives sonesitatug vedotin plus rilvegostomig with capecitabine for PD-L1–positive, ICI-eligible patients, and Cohort 2 receives sonesitatug vedotin with capecitabine for PD-L1–negative or ICI-ineligible patients. CLDN18.2 and PD-L1 status are determined by central immunohistochemistry and the trial also evaluates the clinical performance of the investigational diagnostic tests. Key outcomes include measures of anti-tumor activity and safety on this targeted antibody–drug conjugate combination.

Who should consider this trial

Good fit: Adults with untreated, unresectable or metastatic CLDN18.2-positive, HER2-negative gastric, GEJ, or distal esophageal adenocarcinoma who meet PD-L1 and ECOG 0–1 criteria are eligible.

Not a fit: Patients lacking CLDN18.2 expression, those with HER2-positive tumors, or those unable to tolerate capecitabine or antibody–drug conjugates are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, this regimen could improve tumor response and extend survival for patients with CLDN18.2-positive, HER2-negative advanced gastric, GEJ, or esophageal adenocarcinoma.

How similar studies have performed: Other CLDN18.2-targeted therapies, such as the antibody zolbetuximab, have shown encouraging results, so this ADC approach builds on promising but still emerging evidence.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Capable of giving signed informed consent
* Participant must be 18 years or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the informed consent.
* Previously untreated histologically documented unresectable, locally advanced, or metastatic gastric, GEJ, or distal esophagus (distal third of the esophagus) adenocarcinoma
* Positive CLDN18.2 expression, as determined prospectively by central IHC testing
* Confirmed PD-L1 CPS status by central IHC testing and ICI eligibility per investigator judgement is required to determine cohort eligibility as described below:

  1. Cohort 1: PD-L1 positive as determined by central IHC testing and the participant is deemed ICI eligible per investigator judgement.
  2. Cohort 2: PD-L1 negative as determined by central IHC testing OR the participant is ICI ineligible
* ECOG performance status of 0 or 1 with no deterioration to \> 1 over the previous 2 weeks prior to baseline at screening and prior to randomisation.
* Minimum life expectancy of ≥ 12 weeks.
* At least one lesion (measurable and/or non-measurable) that can be accurately assessed by the investigator based on RECIST 1.1.
* Adequate organ and bone marrow function as specified in the protocol
* Body weight ≥ 35 kg.
* Sex and contraceptive requirements

Exclusion Criteria:

* Known HER2-positive status
* Significant or unstable gastric bleeding and/or untreated gastric ulcers.
* Active or history of autoimmune or inflammatory disorders requiring systemic treatment with steroids or other immunosuppressive treatment or assessed by investigator as not appropriate to participate due to undue risk are excluded.
* CNS pathology
* Clinically significant pleural effusions or ascites and/or pleural effusions or ascites that require drainage, peritoneal shunt, or indwelling catheter/drain.
* Require parenteral nutrition support due to gastric or gastrointestinal obstruction.
* Peripheral neuropathy, sensory or motor, ≥ CTCAE Grade 2 at screening.
* Persistent toxicities caused by previous anticancer therapy excluding alopecia, not yet improved to Grade ≤ 1 or baseline.
* Cardiac abnormalities as outlined in the protocol
* Uncontrolled diabetes or diabetic neuropathy within 3 months prior to randomisation.
* Infectious disease including active hepatitis A infection; uncontrolled hepatitis B and/or chronic or active hepatitis B with HBV DNA ≥ 100 IU/mL; Known chronic, active, or uncontrolled hepatitis C; HIV infection that is not well controlled
* Known partial or total DPD enzyme deficiency

Where this trial is running

Phoenix, Arizona and 257 other locations

+208 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Gastric CancerGastroesophageal Junction AdenocarcinomaEsophageal CancerAdvanced Gastroesophageal Junction Adenocarcinoma,Advanced Gastric Adenocarcinoma,Advanced Esophageal Adenocarcinoma,Metastatic Gastric Adenocarcinoma,Metastatic Gastroesophageal Junction Adenocarcinoma,
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.