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Sonesitatug Vedotin in Combination With Capecitabine With or Without Rilvegostomig in Participants With Advanced or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma Expressing Claudin18.2

RecruitingPhase 3

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)

Who can join

Ages 18 and older · All sexes

Full eligibility 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

About the study

The purpose of this study is to evaluate the efficacy and safety of sonesitatug vedotin in combination with capecitabine with or without rilvegostomig in first-line (1L) Claudin18.2 (CLDN18.2)-positive, human epidermal growth factor receptor 2 (HER2)-negative, gastric, gastroesophageal junction (GEJ), and esophageal adenocarcinoma.

What is being tested

Sponsor: AstraZeneca · Participants: 2,130 · Started: Feb 3, 2026

Contact the study team

Official record on ClinicalTrials.gov — NCT07431281

Locations in the U.S.

AlabamaResearch Site, Birmingham (Not yet recruiting)
Research Site, Mobile (Not yet recruiting)
AlaskaResearch Site, Anchorage (Not yet recruiting)
ArizonaResearch Site, Phoenix
ArkansasResearch Site, Springdale (Not yet recruiting)
CaliforniaResearch Site, Duarte (Not yet recruiting)
Research Site, Fountain Valley (Not yet recruiting)
Research Site, Fullerton (Not yet recruiting)
Research Site, Irvine (Not yet recruiting)
Research Site, La Jolla (Not yet recruiting)
Research Site, Los Alamitos (Not yet recruiting)
Research Site, Orange (Not yet recruiting)
Research Site, Walnut Creek
ColoradoResearch Site, Denver (Not yet recruiting)
Research Site, Lone Tree
DelawareResearch Site, Newark (Not yet recruiting)
FloridaResearch Site, Jacksonville
Research Site, Orlando (Not yet recruiting)
GeorgiaResearch Site, Atlanta
Research Site, Atlanta (Not yet recruiting)
Research Site, Macon (Not yet recruiting)
Research Site, Newnan (Not yet recruiting)
IllinoisResearch Site, Chicago (Not yet recruiting)
Research Site, Niles
Research Site, Zion (Not yet recruiting)
IndianaResearch Site, Indianapolis (Not yet recruiting)
IowaResearch Site, Waukee (Not yet recruiting)
KentuckyResearch Site, Lexington (Not yet recruiting)
Research Site, Louisville (Not yet recruiting)
MarylandResearch Site, Silver Spring (Not yet recruiting)
MassachusettsResearch Site, Boston (Not yet recruiting)
Research Site, Burlington (Not yet recruiting)
MichiganResearch Site, Grand Rapids
MinnesotaResearch Site, Burnsville
Research Site, Duluth (Not yet recruiting)
Research Site, Minneapolis (Not yet recruiting)
Research Site, Rochester (Not yet recruiting)
MissouriResearch Site, Kansas City
Research Site, St Louis
New JerseyResearch Site, Camden (Not yet recruiting)
Research Site, East Brunswick
Research Site, Hackensack (Not yet recruiting)
Research Site, New Brunswick (Not yet recruiting)
Research Site, Summit
New YorkResearch Site, New York (Not yet recruiting)
Research Site, New York (Not yet recruiting)
Research Site, New York
Research Site, The Bronx (Not yet recruiting)
Research Site, The Bronx (Not yet recruiting)
North CarolinaResearch Site, Charlotte
Research Site, Wilmington
Research Site, Winston-Salem
OhioResearch Site, Columbus (Not yet recruiting)
OregonResearch Site, Portland
Research Site, Portland (Not yet recruiting)
PennsylvaniaResearch Site, Hershey (Not yet recruiting)
Research Site, Philadelphia (Not yet recruiting)
Research Site, Pittsburgh
Research Site, Pittsburgh (Not yet recruiting)
Research Site, Wilkes-Barre (Not yet recruiting)
Research Site, York
Rhode IslandResearch Site, Providence (Not yet recruiting)
South CarolinaResearch Site, Charleston (Not yet recruiting)
South DakotaResearch Site, Sioux Falls
Research Site, Yankton
TennesseeResearch Site, Nashville
TexasResearch Site, Dallas (Not yet recruiting)
Research Site, Dallas
Research Site, Houston (Not yet recruiting)
Research Site, Sherman
VirginiaResearch Site, Blacksburg
Research Site, Fairfax
Research Site, Fort Belvoir (Not yet recruiting)
Research Site, Richmond (Not yet recruiting)
WashingtonResearch Site, Edmonds
Research Site, Issaquah
Research Site, Olympia (Not yet recruiting)
Research Site, Seattle
West VirginiaResearch Site, Charleston (Not yet recruiting)
WisconsinResearch Site, Milwaukee (Not yet recruiting)

Conditions

From ClinicalTrials.gov, data retrieved Sep 29, 2026. Each study sets its own eligibility; the study team decides who can join.