Gastric Cancer Clinical Trial
Official title:
A Phase III Multi-center, Open-label, Sponsor-blinded, Randomized Study of AZD0901 Monotherapy Compared With Investigator's Choice of Therapy in Second- or Later-Line Adult Participants With Advanced/Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Claudin18.2
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.
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). |
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 |
Lead Sponsor | Collaborator |
---|---|
AstraZeneca |
United States, Vietnam, Canada, China, France, Germany, Hong Kong, India, Italy, Japan, Poland, Spain, Switzerland, Taiwan, Thailand, United Kingdom,
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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