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NCT07431281PHASE3Recruiting

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

AstraZeneca

Start Date

2/3/2026

Completion Date

10/27/2031

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.

Detailed Description

The purpose of this Phase III study is to evaluate the efficacy and safety of sonesitatug vedotin in combination with capecitabine with or without rilvegostomig in 1L CLDN18.2-positive, HER2-negative gastric, GEJ, and esophageal adenocarcinoma, and the clinical performance of the investigation in vitro diagnostics (IVDs). The study will include 2 cohorts to provide a treatment option for all participants that are HER2-negative and CLDN18.2-positive. Cohort 1 will evaluate sonesitatug vedotin in combination with rilvegostomig with capecitabine in participants who are CLDN18.2-positive and programmed death-ligand 1 (PD-L1) positive. Cohort 2 will evaluate sonesitatug vedotin in combination with capecitabine in participants who are CLDN18.2-positive and PD-L1 negative or immune checkpoint inhibitor (ICI) ineligible.

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

DRUG

Sonesitatug vedotin

DRUG

Rilvegostomig

DRUG

Nivolumab

DRUG

Capecitabine

DRUG

5-Fluorouracil

DRUG

Oxaliplatin

DRUG

Zolbetuximab

DRUG

Leucovorin

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Conditions

Gastric CancerGastroesophageal Junction AdenocarcinomaEsophageal Cancer

Locations

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Mobile, Alabama 36604

United States

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Anchorage, Alaska 99508

United States

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Phoenix, Arizona 85054

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Springdale, Arkansas 72762

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Duarte, California 91010

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Fullerton, California 92835

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La Jolla, California 92093

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Los Alamitos, California 90720

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Orange, California 92868

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Walnut Creek, California 94598

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Denver, Colorado 80210

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Lone Tree, Colorado 80124

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New Haven, Connecticut 06510

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Newark, Delaware 19713

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Washington D.C., District of Columbia 20007

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Fort Myers, Florida 33901

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Jacksonville, Florida 32224

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Orlando, Florida 32806

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St. Petersburg, Florida 33705

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West Palm Beach, Florida 33401

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Atlanta, Georgia 30309

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Atlanta, Georgia 30322

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Atlanta, Georgia 30342

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Macon, Georgia 31201

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Newnan, Georgia 30265

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Chicago, Illinois 60637

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Niles, Illinois 60714

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Zion, Illinois 60099

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Indianapolis, Indiana 46260

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Waukee, Iowa 50263

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Lexington, Kentucky 40536

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Louisville, Kentucky 40217

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Boston, Massachusetts 02114

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Burlington, Massachusetts 01803

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Worcester, Massachusetts 01655

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Grand Rapids, Michigan 49503

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Burnsville, Minnesota 55337

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Duluth, Minnesota 55805

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Rochester, Minnesota 55905

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Kansas City, Missouri 64132

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St Louis, Missouri 63110

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Camden, New Jersey 08103

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East Brunswick, New Jersey 08816

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Hackensack, New Jersey 07601

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New Brunswick, New Jersey 08901

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Summit, New Jersey 07901

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New York, New York 10029

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New York, New York 10032

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New York, New York 10065

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The Bronx, New York 10461

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The Bronx, New York 10468

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White Plains, New York 10601

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Charlotte, North Carolina 28204

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Wilmington, North Carolina 28403

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Winston-Salem, North Carolina 27103

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Cleveland, Ohio 44195

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Columbus, Ohio 43221

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Portland, Oregon 97213

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Portland, Oregon 97239

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Hershey, Pennsylvania 17033

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Philadelphia, Pennsylvania 19104

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Pittsburgh, Pennsylvania 15232

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Pittsburgh, Pennsylvania 15240

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Wilkes-Barre, Pennsylvania 18711

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York, Pennsylvania 17403

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Charleston, South Carolina 29425

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Sioux Falls, South Dakota 57105

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Memphis, Tennessee 38104

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Nashville, Tennessee 37203

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Dallas, Texas 75235

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Dallas, Texas 75246

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Sherman, Texas 75090

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Blacksburg, Virginia 24060

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Fairfax, Virginia 22031

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Falls Church, Virginia 22042

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Fort Belvoir, Virginia 22060

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Richmond, Virginia 23219

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Edmonds, Washington 98026

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Issaquah, Washington 98029

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Olympia, Washington 98502

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Seattle, Washington 98104

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Charleston, West Virginia 25315

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Milwaukee, Wisconsin 53226

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Darlinghurst, 2010

Australia

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Garran, 2605

Australia

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Heidelberg, 3084

Australia

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Murdoch, 6150

Australia

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Randwick, 2031

Australia

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Westmead, 2145

Australia

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Linz, 4010

Austria

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Rankweil, 6830

Austria

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Vienna, 1090

Austria

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Wiener Neustadt, 2700

Austria

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Brussels, 1200

Belgium

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Edegem, 2650

Belgium

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Ghent, 9000

Belgium

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Leuven, 3000

Belgium

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Barretos, 14784-400

Brazil

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Fortaleza, 60336-045

Brazil

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Natal, 59075-740

Brazil

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Porto Alegre, 91350200

Brazil

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Salvador, 41.950-610

Brazil

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Santa Maria, 97015-450

Brazil

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São Paulo, 01246-000

Brazil

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Vitória, 29043-260

Brazil

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Edmonton, Alberta T6G 1Z2

Canada

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Abbotsford British Columbia, British Columbia V2S0C2

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Vancouver, British Columbia VSZ 4E6

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Winnipeg, Manitoba R3E 0V9

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Moncton, New Brunswick E1C 2Z3

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Barrie, Ontario L4M 6M2

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Brampton, Ontario L6R 3J7

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Ottawa, Ontario K1H 8L6

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Sault Ste. Marie, Ontario P6A 0A8

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Toronto, Ontario M4N 3M5

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Toronto, Ontario M5G 2M9

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Montreal, Quebec H3A 1A1

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Québec, Quebec G1J 1Z4

Canada

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Beijing, 100032

China

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Beijing, 100050

China

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Beijing, 100142

China

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Beijing, 102200

China

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Changde, 415000

China

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Chengdu, 610041

China

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Chengdu, 610041

China

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Chongqing, 400016

China

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Fuzhou, 350005

China

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Fuzhou, 350011

China

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Guangzhou, 510655

China

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Hangzhou, 310003

China

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Hangzhou, 310014

China

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Hangzhou, 310020

China

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Harbin, 150081

China

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Hefei, 230031

China

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Hohhot, 010020

China

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Jinan, 2501117

China

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Kunming, 650118

China

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Lanzhou, 730000

China

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Linhai, 317000

China

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Linyi, 276000

China

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Nanchang, 330000

China

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Nanchang, 330029

China

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Nanjing, 2100008

China

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Nanjing, 210029

China

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Nanning, 530021

China

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Nantong, 226361

China

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Shanghai, 200025

China

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Shanghai, 200127

China

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Shanghai, 20032

China

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Shantou, 515041

China

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Shenyang, 110016

China

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Shenzhen, 518036

China

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Tianjin, 300050

China

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Wuhan, 430030

China

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Wuhan, 430079

China

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Xi'an, 710068

China

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Xiamen, 361003

China

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Xingtai, 054031

China

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Xuzhou, 221009

China

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Yinchuan, 750004

China

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Zhengzhou, 450008

China

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Bordeaux, 33000

France

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Caen, 41076

France

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Lyon, 69373

France

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Marseille, 13273

France

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Rennes, 35000

France

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Villejuif, 94805

France

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Augsburg, 86156

Germany

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Bad Saarow, 15526

Germany

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Berlin, 13353

Germany

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Bonn, 53127

Germany

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Dresden, 01370

Germany

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Essen, 45122

Germany

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Essen, 45130

Germany

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Frankfurt, 60488

Germany

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Freiburg im Breisgau, 79106

Germany

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Hamburg, 20249

Germany

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Heidelberg, 69120

Germany

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Heilbronn, 74078

Germany

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Leipzig, 04103

Germany

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Lichtenberg, 10365

Germany

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Magdeburg, 39120

Germany

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Mainz, 55131

Germany

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Mannheim, 68167

Germany

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Marburg, 35043

Germany

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Minden, 32429

Germany

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Moers, 47441

Germany

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München, 81657

Germany

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Stuttgart, 70376

Germany

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Ulm, 89081

Germany

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Budapest, 1083

Hungary

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Budapest, 1122

Hungary

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Debrecen, 4032

Hungary

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Győr, 9024

Hungary

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Gyula, 5700

Hungary

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Nyíregyháza, 4400

Hungary

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Pécs, 7624

Hungary

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Zalaegerszeg, 8900

Hungary

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Ahmedabad, 380060

India

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Bhubaneswar, 751019

India

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Hyderabad, 500032

India

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Mohali, 140901

India

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Mohali, 160055

India

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Mumbai, 400012

India

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New Delhi, 110017

India

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New Delhi, 110060

India

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Varanasi, 221005

India

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Vijayawada, 520002

India

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Visakhapatnam, 530053

India

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Meldola, 47014

Italy

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Milan, 20133

Italy

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Milan, 20141

Italy

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Milan, 20162

Italy

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Padova, 35128

Italy

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Rozzano, 20089

Italy

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Tricase, 73039

Italy

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Bunkyō City, 113-8677

Japan

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Chūōku, 104-0045

Japan

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Hirakata-shi, 573-1191

Japan

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Kashiwa, 277-8577

Japan

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Kitaadachi-gun, 362-0806

Japan

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Kōtoku, 135-8550

Japan

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Kurashiki-shi, 710-8602

Japan

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Nagoya, 464-8681

Japan

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Niigata, 951-8566

Japan

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Osaka, 541-8567

Japan

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Ota-shi, 373-8550

Japan

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Sagamihara-shi, 252-0375

Japan

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Sakai, 590-0197

Japan

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Sendai, 980-8574

Japan

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Shimotsuke-shi, 329-0498

Japan

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Sunto-gun, 411-8777

Japan

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Yokohama, 232-0024

Japan

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Yokohama, 241-8515

Japan

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Groningen, 9713 GZ

Netherlands

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Rotterdam, 3015 GD

Netherlands

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Tilburg, 5022 GC

Netherlands

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Gdansk, 80-219

Poland

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Koszalin, 75-581

Poland

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Krakow, 31-501

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Lublin, 20-080

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Olsztyn, 10-228

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Warsaw, 02-034

Poland

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San Juan, 00921

Puerto Rico

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Daegu, 41404

South Korea

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Hwasun-gun, 58128

South Korea

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Seongnam-si, 13620

South Korea

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Seoul, 03080

South Korea

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Seoul, 03722

South Korea

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Seoul, 05505

South Korea

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Seoul, 06351

South Korea

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Seoul, 06591

South Korea

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Barcelona, 08035

Spain

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Barcelona, 8036

Spain

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Madrid, 28041

Spain

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Pamplona, 31008

Spain

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Santander, 39008

Spain

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Santiago de Compostela, 15706

Spain

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Valencia, 46010

Spain

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Kaohsiung City, 80756

Taiwan

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Kaohsiung City, 83301

Taiwan

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Taichung, 40447

Taiwan

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Taichung, 40705

Taiwan

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Tainan, 704

Taiwan

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Taipei, 10002

Taiwan

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Taipei, 112

Taiwan

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Taoyuan, 333

Taiwan

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Bangkok, 10210

Thailand

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Bangkok, 10700

Thailand

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Dusit, 10300

Thailand

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Hat Yai, 90110

Thailand

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Khon Kaen, 40002

Thailand

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Muang, 22000

Thailand

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Muang, 70000

Thailand

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Ankara, 06530

Turkey (Türkiye)

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Antalya, 07100

Turkey (Türkiye)

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Istanbul, 34098

Turkey (Türkiye)

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Istanbul, 34854

Turkey (Türkiye)

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Medreseboğazı, 01250

Turkey (Türkiye)

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Şahinbey, 27310

Turkey (Türkiye)

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Cambridge, CB2 0QQ

United Kingdom

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Dundee, DD1 9SY

United Kingdom

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Leeds, LS9 7TF

United Kingdom

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London, EC1A 7BE

United Kingdom

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Manchester, M20 4BX

United Kingdom

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Oxford, OX3 7LE

United Kingdom