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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06346392
Other study ID # D9802C00001
Secondary ID
Status Recruiting
Phase Phase 3
First received
Last updated
Start date March 4, 2024
Est. completion date October 9, 2026

Study information

Verified date May 2024
Source AstraZeneca
Contact AstraZeneca Clinical Study Information Center
Phone 1-877-240-9479
Email information.center@astrazeneca.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

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.


Recruitment information / eligibility

Status Recruiting
Enrollment 589
Est. completion date October 9, 2026
Est. primary completion date April 10, 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years to 130 Years
Eligibility 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: 1. Participants with positive CLDN18.2 expression from archival tumor collected within past 24 months or from a fresh biopsy. 2. Participants must undergo local (or have had) HER2 testing by IHC/ISH. 4. Disease progression on or after at least one prior regimen 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, aphasia, or stroke 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).

Study Design


Intervention

Drug:
AZD0901
Participants in the AZD0901 arm 1 will receive dose level 1 AZD0901 IV
AZD0901
Participants in the AZD0901 arm 2 will receive dose level 2 AZD0901 IV
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
Paclitaxel
Paclitaxel 80 mg/m2 IV on Days 1, 8, and 15, Q4W (for participants with contraindication to ramucirumab only)
Docetaxel
Docetaxel 75-100 mg/m2 IV on Day 1, Q3W (for participants with contraindication to ramucirumab only)
Irinotecan
Irinotecan 150-180 mg/m2 IV on Days 1 and 15, Q4W
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)
Apatinib
Apatinib 500-850 mg at Investigator's discretion based on participant's condition and tolerability, orally once daily, Q4W (China only)

Locations

Country Name City State
Canada Research Site Barrie Ontario
Canada Research Site Calgary Alberta
Canada Research Site London Ontario
Canada Research Site Montreal Quebec
Canada Research Site North York Ontario
Canada Research Site Ottawa Ontario
Canada Research Site Toronto Ontario
China Research Site Beijing
China Research Site Changsha
China Research Site Chengdu
China Research Site Chengdu
China Research Site Fuzhou
China Research Site Fuzhou City
China Research Site Guangzhou
China Research Site Guangzhou
China Research Site Guangzhou
China Research Site Guangzhou
China Research Site Hangzhou
China Research Site Hangzhou
China Research Site Harbin
China Research Site Hefei
China Research Site Jinan
China Research Site Jining
China Research Site Lanzhou
China Research Site Lishui
China Research Site Luoyang
China Research Site Nanjing
China Research Site Nanjing
China Research Site Qingdao
China Research Site Shanghai
China Research Site Shanghai
China Research Site Shanghai
China Research Site Shenyang
China Research Site Shijiazhuang
China Research Site Suzhou
China Research Site Tianjin
China Research Site Urumqi
China Research Site Wuhan
China Research Site Wuhan
China Research Site Xi'an
China Research Site Yinchuan
China Research Site Zhengzhou
France Research Site Besançon Cedex
France Research Site Brest
France Research Site Lille
France Research Site Lyon
France Research Site Nantes
France Research Site PARIS Cedex 12
France Research Site Poitiers
Germany Research Site Berlin
Germany Research Site Berlin
Germany Research Site Dresden
Germany Research Site Essen
Germany Research Site Frankfurt
Germany Research Site Göttingen
Germany Research Site Hamburg
Germany Research Site Heidelberg
Germany Research Site Heilbronn
Germany Research Site Leipzig
Germany Research Site Mainz
Germany Research Site Marburg
Germany Research Site Moers
Germany Research Site München
Hong Kong Research Site Hong Kong
Hong Kong Research Site Hong Kong
India Research Site Ahmedabad
India Research Site Bengaluru
India Research Site Hyderabad
India Research Site Mumbai
India Research Site New Delhi
Italy Research Site Florence
Italy Research Site Milan
Italy Research Site Milano
Italy Research Site Modena
Italy Research Site Napoli
Italy Research Site Padova
Italy Research Site Pisa
Italy Research Site Vicenza
Japan Research Site Kashiwa
Japan Research Site Tokyo
Poland Research Site Gdansk
Poland Research Site Katowice
Poland Research Site Kraków
Poland Research Site Lublin
Poland Research Site Szczecin
Poland Research Site Tomaszów Mazowiecki
Poland Research Site Warszawa
Spain Research Site Barcelona
Spain Research Site Barcelona
Spain Research Site Madrid
Spain Research Site Madrid
Spain Research Site Orense
Spain Research Site Santander
Spain Research Site Sevilla
Switzerland Research Site Bern
Switzerland Research Site Genève 14
Switzerland Research Site Lausanne
Switzerland Research Site Zürich
Taiwan Research Site Kaohsiung
Taiwan Research Site Kaohsiung
Taiwan Research Site Taichung
Taiwan Research Site Tainan
Taiwan Research Site Taipei
Taiwan Research Site Taipei
Taiwan Research Site Taoyuan
Thailand Research Site Bangkok
Thailand Research Site Dusit
Thailand Research Site Hat Yai
Thailand Research Site Khon-Kaen
United Kingdom Research Site Cambridge
United Kingdom Research Site London
United Kingdom Research Site London
United Kingdom Research Site Manchester
United Kingdom Research Site Oxford
United Kingdom Research Site Taunton
United States Research Site Ann Arbor Michigan
United States Research Site Atlanta Georgia
United States Research Site Baltimore Maryland
United States Research Site Birmingham Alabama
United States Research Site Boise Idaho
United States Research Site Boston Massachusetts
United States Research Site Charlottesville Virginia
United States Research Site Cincinnati Ohio
United States Research Site Duarte California
United States Research Site Fullerton California
United States Research Site Hollywood Florida
United States Research Site Kansas City Missouri
United States Research Site Lexington Kentucky
United States Research Site Los Angeles California
United States Research Site Los Angeles California
United States Research Site Marietta Georgia
United States Research Site Mineola New York
United States Research Site Mobile Alabama
United States Research Site New York New York
United States Research Site New York New York
United States Research Site New York New York
United States Research Site Olympia Washington
United States Research Site Orlando Florida
United States Research Site Philadelphia Pennsylvania
United States Research Site Portland Oregon
United States Research Site Saint Louis Missouri
United States Research Site Saint Louis Missouri
United States Research Site Santa Rosa California
United States Research Site Seattle Washington
United States Research Site Tucson Arizona
United States Research Site Washington District of Columbia
Vietnam Research Site Hanoi
Vietnam Research Site Ho Chi Minh
Vietnam Research Site Ho Chi Minh city
Vietnam Research Site Vinh

Sponsors (1)

Lead Sponsor Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Canada,  China,  France,  Germany,  Hong Kong,  India,  Italy,  Japan,  Poland,  Spain,  Switzerland,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Progression Free Survival (PFS) in all randomized participants The analysis will include all randomized participants. All events will be included, regardless of whether the participant withdraws from therapy or receives another anticancer therapy. From date of first dose/randomisation until disease progression or death in the absence of progression (approximately 3 years).
Primary Overall Survival (OS) for 3L+ participants The analysis will include all randomized participants who had at least 2 prior lines of systemic therapy. All deaths will be included, regardless of whether the participant withdraws from therapy or receives another anticancer therapy. From date of first dose/randomisation until the date of death due to any cause (approximately 3 years).
Secondary OS in all randomized participants The analysis will include all randomized participants. All deaths will be included, regardless of whether the participant withdraws from therapy or receives another anticancer therapy. From date of first dose/randomisation until the date of death due to any cause (approximately 3 years).
Secondary PFS for 3L+ participants The analysis will include all randomized participants who had at least 2 prior lines of systemic therapy. All events will be included, regardless of whether the participant withdraws from therapy or receives another anticancer therapy. From date of first dose/randomisation until disease progression or death in the absence of progression (approximately 3 years).
Secondary Objective Response Rate (ORR) in all randomized participants ORR is defined as the proportion of participants with at least one visit response of confirmed CR or confirmed PR, as determined by BICR per RECIST 1.1. From date of first dose of AZD0901 up until progression, or the last evaluable assessment in the absence of progression (approximately 3 years).
Secondary ORR for 3L+ participants The analysis will include all randomized participants who had at least 2 prior lines of systemic therapy, with measurable disease at baseline From date of first dose of AZD0901 up until progression, or the last evaluable assessment in the absence of progression (approximately 3 years).
Secondary Duration of Response (DoR) in all randomized participants The analysis will include all randomized participants with measurable disease at baseline who have a confirmed response. All events after achieving confirmed response will be included, regardless of whether the participant withdraws from therapy, receives another anticancer therapy or clinically progresses prior to RECIST 1.1. From the date of first documented confirmed response until date of documented progression (approximately 3 years).
Secondary Serum concentrations of AZD0901, total antibody and MMAE To characterise the PK of AZD0901 in participants. From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.
Secondary Status of ADA to AZD0901 To determine the immunogenicity of AZD0901 in participants. From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.
Secondary Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]. Changes from baseline in vital signs, clinical laboratory results, and ECGs To assess the safety and tolerability of AZD0901 as compared with Investigator's choice of therapy in all randomized participants who have received at least one dose of study intervention From start through 30 days post treatment completion and follow up for 90 days.
Secondary PK parameters (such as peak concentration, as data allow) of AZD0901, total antibody and MMAE To characterise the PK of AZD0901 in participants. From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.
Secondary PK parameters (such as trough concentration, as data allow) of AZD0901, total antibody and MMAE To characterise the PK of AZD0901 in participants. From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.
Secondary Prevalence and incidence of ADA to AZD0901 To determine the immunogenicity of AZD0901 in participants. From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.
Secondary Titer of ADA to AZD0901 To determine the immunogenicity of AZD0901 in participants. From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.
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