Recruiting
Phase 3

Sonesitatug Vedotin & Capecitabine

Sponsor:

AstraZeneca

Code:

NCT07431281

Conditions

Gastric Cancer

Gastroesophageal Junction Adenocarcinoma

Esophageal Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Sonesitatug vedotin

Rilvegostomig

Nivolumab

Capecitabine

5-Fluorouracil

Study Details

Brief summary:

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.

Conditions

Gastric Cancer

Gastroesophageal Junction Adenocarcinoma

Esophageal Cancer

Study ID

NCT07431281

Start date

Feb 3, 2026

Status verified date

Oct, 2026

Completion date

Oct 27, 2031

Anticipated

Primary completion date

Aug 16, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

2130 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A

Sonesitatug vedotin + Rilvegostomig + Capecitabine

experimental: Arm B

Sonesitatug vedotin + Nivolumab + Capecitabine

active comparator: Arm C

Nivolumab + CAPOX OR Nivolumab + FOLFOX

  • nivolumab, capecitabine, oxaliplatin
  • nivolumab, 5-Fluorouracil, leucovorin, oxaliplatin

experimental: Arm D

Sonesitatug vedotin + Capecitabine

active comparator: Arm E

Zolbetuximab + CAPOX or Zolbetuximab + FOLFOX:

  • zolbetuximab, capecitabine, oxaliplatin
  • zolbetuximab, 5-Fluorouracil, leucovorin, oxaliplatin

CAPOX or FOLFOX:

  • oxaliplatin, capecitabine,
  • 5-Fluorouracil, leucovorin, oxaliplatin

Interventions

Sonesitatug vedotin

Intravenous

Rilvegostomig

Intravenous

Nivolumab

Intravenous

Capecitabine

Oral

5-Fluorouracil

Intravenous

Oxaliplatin

Intravenous

Zolbetuximab

Intravenous

Leucovorin

Intravenous

Primary outcome measure

  • Progression Free Survival (PFS) (Cohort 1 and Cohort 2) [ Time Frame: Up to approximately 5 years ]
  • Overall Survival (OS) (Cohort 1) [ Time Frame: Up to approximately 5 years ]

Central Contacts and Locations

Central contacts

AstraZeneca Clinical Study Information Center

1-877-240-9479information.center@astrazeneca.com

Locations

Research Site

Recruiting

Phoenix, Arizona, United States, 85054

Research Site

Recruiting

Fountain Valley, California, United States, 92708

Research Site

Recruiting

Irvine, California, United States, 92612

Research Site

Recruiting

La Jolla, California, United States, 92093

Research Site

Recruiting

Orange, California, United States, 92868

Research Site

Recruiting

Walnut Creek, California, United States, 94598

Research Site

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Lone Tree, Colorado, United States, 80124

Research Site

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Jacksonville, Florida, United States, 32224

Research Site

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Atlanta, Georgia, United States, 30309

Research Site

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Atlanta, Georgia, United States, 30322

Research Site

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Macon, Georgia, United States, 31201

Research Site

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Niles, Illinois, United States, 60714

Research Site

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Indianapolis, Indiana, United States, 46260

Research Site

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Grand Rapids, Michigan, United States, 49503

Research Site

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Burnsville, Minnesota, United States, 55337

Research Site

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Rochester, Minnesota, United States, 55905

Research Site

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Kansas City, Missouri, United States, 64132

Research Site

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St Louis, Missouri, United States, 63110

Research Site

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East Brunswick, New Jersey, United States, 08816

Research Site

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Summit, New Jersey, United States, 07901

Research Site

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New York, New York, United States, 10065

Research Site

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The Bronx, New York, United States, 10468

Research Site

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Charlotte, North Carolina, United States, 28204

Research Site

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Wilmington, North Carolina, United States, 28403

Research Site

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Winston-Salem, North Carolina, United States, 27103

Research Site

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Portland, Oregon, United States, 97213

Research Site

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Philadelphia, Pennsylvania, United States, 19104

Research Site

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Pittsburgh, Pennsylvania, United States, 15232

Research Site

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Wilkes-Barre, Pennsylvania, United States, 18711

Research Site

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York, Pennsylvania, United States, 17403

Research Site

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Sioux Falls, South Dakota, United States, 57105

Research Site

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Yankton, South Dakota, United States, 57078

Research Site

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Nashville, Tennessee, United States, 37203

Research Site

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Dallas, Texas, United States, 75246

Research Site

Recruiting

Sherman, Texas, United States, 75090

Research Site

Recruiting

Blacksburg, Virginia, United States, 24060

Research Site

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Fairfax, Virginia, United States, 22031

Research Site

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Richmond, Virginia, United States, 23219

Research Site

Recruiting

Edmonds, Washington, United States, 98026

Research Site

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Issaquah, Washington, United States, 98029

Research Site

Recruiting

Seattle, Washington, United States, 98104

Research Site

Recruiting

Abbotsford British Columbia, British Columbia, Canada, V2S0C2

Research Site

Recruiting

Moncton, New Brunswick, Canada, E1C 2Z3

Research Site

Recruiting

Barrie, Ontario, Canada, L4M 6M2

Research Site

Recruiting

Brampton, Ontario, Canada, L6R 3J7

Research Site

Recruiting

Ottawa, Ontario, Canada, K1H 8L6

Research Site

Recruiting

Sault Ste. Marie, Ontario, Canada, P6A 0A8

Research Site

Recruiting

Toronto, Ontario, Canada, M4N 3M5

Research Site

Recruiting

Toronto, Ontario, Canada, M5G 2M9

Research Site

Recruiting

Montreal, Quebec, Canada, H3A 1A1

Research Site

Recruiting

Québec, Quebec, Canada, G1J 1Z4

More Information

Sponsor

AstraZeneca

Last update posted

Oct 16, 2026

Last verified

Oct, 2026

Keywords

  • Advanced Gastroesophageal Junction (GEJ) Adenocarcinoma,
  • Advanced Gastric Adenocarcinoma,
  • Advanced Esophageal Adenocarcinoma,
  • Metastatic Gastric Adenocarcinoma,
  • Metastatic Gastroesophageal Junction (GEJ) Adenocarcinoma,
  • Metastatic Esophageal Adenocarcinoma,
  • Claudin 18.2,
  • PD-L1,
  • Human epidermal growth factor receptor 2 (HER2) Negative

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-23. This information was provided to ClinicalTrials.gov by AstraZeneca on 2026-10-16. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.