AZD0901 Compared With Investigator's Choice of Therapy in Participants With Second- or Later-line Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Claudin18.2

NCT ID: NCT06346392

Last Updated: 2025-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

572 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-04

Study Completion Date

2026-09-14

Brief Summary

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The purpose of this study is to measure the efficacy and safety of AZD0901 compared to Investigator's choice of therapy as 2L+ treatment for participants with advanced or metastatic gastric or GEJ adenocarcinoma expressing CLDN18.2.

Detailed Description

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This is a Phase III, multi-center, open-label, sponsor-blinded, randomized, global study to assess the efficacy and safety of AZD0901 compared to Investigator's choice of therapy as the 2L+ treatment for participants with advanced or metastatic gastric or GEJ adenocarcinoma expressing CLDN18.2, and the clinical performance of the investigational IVD. As part of this combined approach, the efficacy analyses from this study will also provide the basis to evaluate the clinical performance of Ventana CLDN18.2 assay as an IVD device for the identification of patients with advanced or metastatic gastric or GEJ adenocarcinoma expressing CLDN18.2 who may benefit from AZD0901.

Conditions

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Gastric Cancer Gastroesophageal Junction Cancer

Keywords

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Gastric cancer Gastroesophageal junction cancer Phase III Claudin 18.2 AZD0901

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants were randomized in a 1:1:1 ratio to one of the following intervention arms until the dose selection decision was made. Randomization will continue in a 1:1 ratio to the 2 remaining arms:

Arm 1: AZD0901 arm 1 IV, Q3W Arm 2: AZD0901 arm 2 IV, Q3W (Enrolment was closed) Arm 3: Participants in the Investigator's choice arm, including regionally accepted chemotherapies or targeted therapies 2L: Ramucirumab 8 mg/kg IV on Days 1 and 15 and paclitaxel 80 mg/m2 IV on Days 1, 8, and 15, Q4W 2L: Paclitaxel 80 mg/m2 IV on Days 1, 8, and 15, Q4W (for participants with contraindication to ramucirumab only) 2L: Docetaxel 75-100 mg/m2 IV on Day 1, Q3W (for participants with contraindication to ramucirumab only) 3L+: Irinotecan 150-180 mg/m2 IV on Days 1 and 15, Q4W 3L+: TAS-102 35 mg/m2 up to a maximum of 80 mg orally twice a day on Days 1 to 5 and Days 8 to 12, Q4W (except China) 3L+: Apatinib 500-850 mg, orally once daily, Q4W (China only)
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
This is an open-label study; however, it will be conducted 'sponsor-blind' and the specific treatment to be taken by a participant will be assigned using an IRT/RTSM. To maintain the integrity of the study, sponsor access to treatment records will be restricted, and, in particular, under no circumstances will the sponsor undertake any efficacy analysis by treatment arm during the study. A Study Integrity Plan will be generated in which nominated individuals who will be granted access to any treatment-revealing data will be pre-specified, with their reason for requiring access detailed.

Study Groups

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AZD0901 arm 1

Participants in the AZD0901 arm 1 will receive AZD0901 dose level 1 intravenous infusion treatment.

Group Type EXPERIMENTAL

AZD0901

Intervention Type DRUG

Participants in the AZD0901 arm 1 will receive dose level 1 AZD0901 IV

AZD0901 Arm 2

Participants in the AZD0901 arm 2 will receive AZD0901 dose level 2 intravenous infusion treatment. (Enrolment was closed)

Group Type EXPERIMENTAL

AZD0901

Intervention Type DRUG

Participants in the AZD0901 arm 2 will receive dose level 2 AZD0901 IV (Enrolment was closed)

Investigator's choice arm

Participants in the Investigator's choice arm will receive a regimen of Investigator's choice, including regionally accepted chemotherapies or targeted therapies.

Group Type ACTIVE_COMPARATOR

Ramucirumab+ paclitaxel

Intervention Type DRUG

Ramucirumab 8 mg/kg IV on Days 1 and 15 and paclitaxel 80 mg/m2 IV on Days 1, 8, and 15, Q4W

Paclitaxel

Intervention Type DRUG

Paclitaxel 80 mg/m2 IV on Days 1, 8, and 15, Q4W (for participants with contraindication to ramucirumab only)

Docetaxel

Intervention Type DRUG

Docetaxel 75-100 mg/m2 IV on Day 1, Q3W (for participants with contraindication to ramucirumab only)

Irinotecan

Intervention Type DRUG

Irinotecan 150-180 mg/m2 IV on Days 1 and 15, Q4W

TAS-102

Intervention Type DRUG

TAS-102 35 mg/m2 up to a maximum of 80 mg orally twice a day on Days 1 to 5 and Days 8 to 12, Q4W (except China)

Apatinib

Intervention Type DRUG

Apatinib 500-850 mg at Investigator's discretion based on participant's condition and tolerability, orally once daily, Q4W (China only)

Interventions

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AZD0901

Participants in the AZD0901 arm 1 will receive dose level 1 AZD0901 IV

Intervention Type DRUG

AZD0901

Participants in the AZD0901 arm 2 will receive dose level 2 AZD0901 IV (Enrolment was closed)

Intervention Type DRUG

Ramucirumab+ paclitaxel

Ramucirumab 8 mg/kg IV on Days 1 and 15 and paclitaxel 80 mg/m2 IV on Days 1, 8, and 15, Q4W

Intervention Type DRUG

Paclitaxel

Paclitaxel 80 mg/m2 IV on Days 1, 8, and 15, Q4W (for participants with contraindication to ramucirumab only)

Intervention Type DRUG

Docetaxel

Docetaxel 75-100 mg/m2 IV on Day 1, Q3W (for participants with contraindication to ramucirumab only)

Intervention Type DRUG

Irinotecan

Irinotecan 150-180 mg/m2 IV on Days 1 and 15, Q4W

Intervention Type DRUG

TAS-102

TAS-102 35 mg/m2 up to a maximum of 80 mg orally twice a day on Days 1 to 5 and Days 8 to 12, Q4W (except China)

Intervention Type DRUG

Apatinib

Apatinib 500-850 mg at Investigator's discretion based on participant's condition and tolerability, orally once daily, Q4W (China only)

Intervention Type DRUG

Other Intervention Names

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Sonesitatug Vedotin Sonesitatug Vedotin

Eligibility Criteria

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Inclusion Criteria

1. Capable of giving signed informed consent prior to any study procedure.
2. Participant must be at least 18 years or the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the ICF.
3. Histologically confirmed unresectable, locally advanced or metastatic adenocarcinoma of gastric, GEJ, or distal esophagus (distal third of the esophagus) and the following requirement:

(a) Participants with positive CLDN18.2 expression from archival tumor collected within past 24 months or from a fresh biopsy.
4. Disease progression on or after at least one prior line of treatment (LoT) for advanced or metastatic disease, which included a fluoropyrimidine and a platinum, for advanced or metastatic disease.
5. Must have at least one measurable or evaluable lesion assessed by the Investigator based on RECIST 1.1.
6. ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
7. Predicted life expectancy of ≥ 12 weeks.
8. Adequate organ and bone marrow function
9. Body weight of ≥ 35 kg.
10. Sex and Contraceptive Requirements

Exclusion Criteria

1. Participants with known HER2 positive status as defined as IHC 3+ or IHC 2+/ISH + (Cases with HER2: CEP17 ratio ≥ 2 or an average HER2 copy number ≥ 6.0 signals/cell are considered positive by ISH). Participants must undergo local (or have had) HER2 testing by IHC/ISH, and the most recent result of HER2 status will be used to determine the eligibility.
2. Participant has significant or unstable gastric bleeding and/or untreated gastric ulcers.
3. CNS metastases or CNS pathology including: epilepsy, seizures or aphasia within 3 months prior to consent, severe brain injury, dementia, Parkinson's disease, neurodegenerative diseases, cerebellar disease, severe uncontrolled mental illness, psychosis, CNS involvement of autoimmune diseases.
4. Participant has known clinically significant corneal disease (eg, active keratitis or corneal ulcerations).
5. Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anticancer therapy, excluding alopecia. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention may be included (eg, hearing loss).
6. Prior exposure to any ADC with MMAE payload or any CLDN18.2 targeting treatment other than naked monoclonal antibody (eg, CLDN18.2 targeting CAR-T cell therapy, multi-specific antibody including targeting CLDN18.2, etc).
7. History of thromboembolic events:

1. Participants with venous thromboembolism within the past 6 months prior to randomization: participants with venous port or catheter thrombosis or superficial venous thrombus that do not require treatment or are stable on treatment with anticoagulants are excepted
2. History of arterial thromboembolism within the past 12 months prior to randomization
8. As judged by the Investigator, any evidence of diseases which in the Investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Birmingham, Alabama, United States

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Mobile, Alabama, United States

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Tucson, Arizona, United States

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Duarte, California, United States

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Fullerton, California, United States

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Irvine, California, United States

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Los Angeles, California, United States

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Los Angeles, California, United States

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Newport Beach, California, United States

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Santa Rosa, California, United States

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

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Fleming Island, Florida, United States

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Hollywood, Florida, United States

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Orlando, Florida, United States

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Atlanta, Georgia, United States

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Marietta, Georgia, United States

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Honolulu, Hawaii, United States

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Boise, Idaho, United States

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Lexington, Kentucky, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Ann Arbor, Michigan, United States

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Kansas City, Missouri, United States

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St Louis, Missouri, United States

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St Louis, Missouri, United States

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Mineola, New York, United States

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New York, New York, United States

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New York, New York, United States

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New York, New York, United States

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Cincinnati, Ohio, United States

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Portland, Oregon, United States

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Philadelphia, Pennsylvania, United States

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York, Pennsylvania, United States

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Charlottesville, Virginia, United States

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Fredericksburg, Virginia, United States

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Olympia, Washington, United States

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Seattle, Washington, United States

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Porto Alegre, , Brazil

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Ribeirão Preto, , Brazil

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São Paulo, , Brazil

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Vitória, , Brazil

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Calgary, Alberta, Canada

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Barrie, Ontario, Canada

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London, Ontario, Canada

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North York, Ontario, Canada

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Ottawa, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Beijing, , China

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Changchun, , China

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Changsha, , China

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Chengdu, , China

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Chengdu, , China

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Fuzhou, , China

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Fuzhou, , China

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Guangzhou, , China

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Guangzhou, , China

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Guangzhou, , China

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Guangzhou, , China

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Hangzhou, , China

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Hangzhou, , China

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Harbin, , China

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Hefei, , China

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Hefei, , China

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Hefei, , China

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Jinan, , China

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Jining, , China

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Lanzhou, , China

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Lishui, , China

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Luoyang, , China

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Nanjing, , China

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Nanjing, , China

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Qingdao, , China

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Shanghai, , China

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Shanghai, , China

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Shanghai, , China

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Shenyang, , China

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Shijiazhuang, , China

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Suzhou, , China

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Tianjin, , China

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Ürümqi, , China

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Wuhan, , China

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Wuhan, , China

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Xi'an, , China

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Yinchuan, , China

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Zhengzhou, , China

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Besançon, , France

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Brest, , France

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Lille, , France

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Lyon, , France

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Nantes, , France

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Paris, , France

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Poitiers, , France

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Berlin, , Germany

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Berlin, , Germany

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Dresden, , Germany

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Dresden, , Germany

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Essen, , Germany

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Frankfurt, , Germany

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Göttingen, , Germany

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Hamburg, , Germany

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Heidelberg, , Germany

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Heilbronn, , Germany

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Leipzig, , Germany

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Mainz, , Germany

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Marburg, , Germany

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Moers, , Germany

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München, , Germany

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Hong Kong, , Hong Kong

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Hong Kong, , Hong Kong

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Ahmedabad, , India

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Bengaluru, , India

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Hyderabad, , India

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Mumbai, , India

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New Delhi, , India

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Florence, , Italy

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Milan, , Italy

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Milan, , Italy

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Modena, , Italy

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Napoli, , Italy

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Padua, , Italy

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Pisa, , Italy

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Vicenza, , Italy

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Fukuoka, , Japan

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Kashiwa, , Japan

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Kōtoku, , Japan

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Nagoya, , Japan

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Ogaki-shi, , Japan

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Osaka, , Japan

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Sunto-gun, , Japan

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Tokyo, , Japan

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Toyoake-shi, , Japan

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Yokohama, , Japan

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Bielsko-Biala, , Poland

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Gdansk, , Poland

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Katowice, , Poland

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Krakow, , Poland

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Lublin, , Poland

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Szczecin, , Poland

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Słupsk, , Poland

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Tomaszów Mazowiecki, , Poland

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Warsaw, , Poland

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Warsaw, , Poland

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Gyeonggi-do, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Barcelona, , Spain

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Barcelona, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Ourense, , Spain

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Santander, , Spain

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Seville, , Spain

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Bern, , Switzerland

Site Status ACTIVE_NOT_RECRUITING

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Geneva, , Switzerland

Site Status ACTIVE_NOT_RECRUITING

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Lausanne, , Switzerland

Site Status ACTIVE_NOT_RECRUITING

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Zurich, , Switzerland

Site Status ACTIVE_NOT_RECRUITING

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Kaohsiung City, , Taiwan

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Kaohsiung City, , Taiwan

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Taichung, , Taiwan

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Tainan, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taoyuan District, , Taiwan

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Bangkok, , Thailand

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Dusit, , Thailand

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Hat Yai, , Thailand

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Khon Kaen, , Thailand

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Ankara, , Turkey (Türkiye)

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Diyarbakır, , Turkey (Türkiye)

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Erzurum, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Cambridge, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Oxford, , United Kingdom

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Taunton, , United Kingdom

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Hanoi, , Vietnam

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Ho Chi Minh City, , Vietnam

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Vinh, , Vietnam

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Countries

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United States Brazil Canada China France Germany Hong Kong India Italy Japan Poland South Korea Spain Switzerland Taiwan Thailand Turkey (Türkiye) United Kingdom Vietnam

Central Contacts

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AstraZeneca Clinical Study Information Center

Role: CONTACT

Phone: 1-877-240-9479

Email: [email protected]

References

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Xu G, Liu W, Wang Y, Wei X, Liu F, He Y, Zhang L, Song Q, Li Z, Wang C, Xu R, Chen B. CMG901, a Claudin18.2-specific antibody-drug conjugate, for the treatment of solid tumors. Cell Rep Med. 2024 Sep 17;5(9):101710. doi: 10.1016/j.xcrm.2024.101710. Epub 2024 Sep 3.

Reference Type DERIVED
PMID: 39232496 (View on PubMed)

Other Identifiers

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2023-508276-11-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

D9802C00001

Identifier Type: -

Identifier Source: org_study_id