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)

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Investigational drug late phase More information Active drug More information Moderate burden on patient More information

Trial Details

Sponsor: AstraZeneca (industry)

Phase: 3

Start date: Feb. 3, 2026

Planned enrollment: 2130

Trial ID: NCT07431281
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More trial details at ClinicalTrials.gov More info

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Investigational Drug AI Analysis

chevron Show for: Rilvegostomig (AZD2936)

chevron Show for: AZD0901 (Sonesitatug vedotin, CMG901)

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Goal: Evaluate whether first-line sonesitatug vedotin plus capecitabine, with or without an immune-checkpoint inhibitor, improves outcomes in CLDN18.2-positive, HER2-negative advanced gastroesophageal adenocarcinoma while assessing safety and diagnostic test performance.

Patients: Adults with previously untreated, unresectable locally advanced or metastatic gastric, gastroesophageal junction, or distal esophageal adenocarcinoma; centrally confirmed CLDN18.2 positivity and PD-L1 status; ECOG performance status 0–1; and adequate organ function. Cohort 1 includes PD-L1-positive, checkpoint-inhibitor-eligible patients. Cohort 2 includes PD-L1-negative or checkpoint-inhibitor-ineligible patients.

Design: Multicentre, randomized controlled trial with two cohorts assigned according to PD-L1 status and checkpoint-inhibitor eligibility. Investigational regimens are compared with active treatment regimens appropriate to each cohort.

Treatments: Cohort 1 evaluates sonesitatug vedotin plus capecitabine with either rilvegostomig or nivolumab, against nivolumab plus CAPOX or FOLFOX. Cohort 2 evaluates sonesitatug vedotin plus capecitabine against zolbetuximab plus CAPOX or FOLFOX, or CAPOX or FOLFOX alone. Sonesitatug vedotin is a CLDN18.2-directed antibody–drug conjugate that delivers the microtubule-disrupting agent MMAE into target cells. Single-arm studies in previously treated gastric or gastroesophageal junction cancer reported response rates of approximately 28%; those results do not establish first-line benefit. Rilvegostomig is an investigational bispecific antibody blocking PD-1 and TIGIT to enhance antitumor immune activity. Early single-arm lung cancer studies reported responses, but have not established superiority over available checkpoint inhibitors or efficacy in this disease. Nivolumab is a PD-1 inhibitor; zolbetuximab targets CLDN18.2; CAPOX and FOLFOX are oxaliplatin-based chemotherapy regimens.

Outcomes: Primary endpoints are RECIST 1.1 progression-free survival in both cohorts and overall survival in cohort 1. Secondary measures include cohort 2 overall survival, additional cohort 1 comparisons of nivolumab-containing arms, objective response rate, duration of response, adverse events, and pharmacokinetics and immunogenicity of the investigational drugs. Outcomes may be assessed for up to approximately five years.

Burden on patient: Moderate. Central CLDN18.2 and PD-L1 testing is required, and participants will need treatment visits, repeated imaging and safety assessments, and blood draws for pharmacokinetics and immunogenicity. Intravenous combination regimens and long-term follow-up add travel and monitoring compared with routine oral therapy. The protocol information provided does not specify imaging or blood-draw frequency or require additional research biopsies.

Last updated: Sep 2026

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Status: Not yet recruiting

Research Site

Fort Belvoir, Virginia, 22060, United States

No email / No phone

Status: Not yet recruiting

Research Site

Richmond, Virginia, 23219, United States

No email / No phone

Status: Not yet recruiting

Research Site

Seattle, Washington, 98104, United States

No email / No phone

Status: Not yet recruiting

Research Site

Olympia, Washington, 98502, United States

No email / No phone

Status: Not yet recruiting

Research Site

Charleston, West Virginia, 25315, United States

No email / No phone

Status: Not yet recruiting

Research Site

Milwaukee, Wisconsin, 53226, United States

No email / No phone

Status: Not yet recruiting

Research Site

Rankweil, 6830, Austria

No email / No phone

Status: Withdrawn

Research Site

Linz, 4010, Austria

No email / No phone

Status: Withdrawn

Research Site

Wiener Neustadt, 2700, Austria

No email / No phone

Status: Withdrawn

Research Site

Vienna, 1090, Austria

No email / No phone

Status: Withdrawn

Research Site

Winnipeg, Manitoba, R3E 0V9, Canada

No email / No phone

Status: Withdrawn

Research Site

Mannheim, 68167, Germany

No email / No phone

Status: Withdrawn

Research Site

Heidelberg, 69120, Germany

No email / No phone

Status: Withdrawn

Research Site

Varanasi, 221005, India

No email / No phone

Status: Withdrawn

Research Site

New Delhi, 110060, India

No email / No phone

Status: Withdrawn

Research Site

New Haven, Connecticut, 06510, United States

No email / No phone

Status: Withdrawn

Research Site

Washington D.C., District of Columbia, 20007, United States

No email / No phone

Status: Withdrawn

Research Site

St. Petersburg, Florida, 33705, United States

No email / No phone

Status: Withdrawn

Research Site

West Palm Beach, Florida, 33401, United States

No email / No phone

Status: Withdrawn

Research Site

Fort Myers, Florida, 33901, United States

No email / No phone

Status: Withdrawn

Research Site

Atlanta, Georgia, 30342, United States

No email / No phone

Status: Withdrawn

Research Site

New York, New York, 10029, United States

No email / No phone

Status: Withdrawn

Research Site

White Plains, New York, 10601, United States

No email / No phone

Status: Withdrawn

Research Site

Cleveland, Ohio, 44195, United States

No email / No phone

Status: Withdrawn

Research Site

Memphis, Tennessee, 38104, United States

No email / No phone

Status: Withdrawn

Research Site

Falls Church, Virginia, 22042, United States

No email / No phone

Status: Withdrawn

Research Site

Darlinghurst, 2010, Australia

No email / No phone

Status: SUSPENDED

Research Site

Garran, 2605, Australia

No email / No phone

Status: SUSPENDED

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