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

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• Research Site
  Phoenix, Arizona, United States Recruiting
• Research Site
  Fountain Valley, California, United States Recruiting
• Research Site
  Irvine, California, United States Recruiting
• Research Site
  La Jolla, California, United States Recruiting
• Research Site
  Orange, California, United States Recruiting
• Research Site
  Walnut Creek, California, United States Recruiting

+264 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: AstraZeneca Clinical Study Information Center
• Email: information.center@astrazeneca.com
• Phone: 1-877-240-9479

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.