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

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06346392
• Other study ID #: D9802C00001
• Status: Recruiting
• Phase: Phase 3
• Start date: March 4, 2024
• Est. completion date: October 9, 2026

Study information

• Verified date: March 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• 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).

Related Conditions & MeSH terms

• Adenocarcinoma
• Gastric Cancer
• Gastroesophageal Junction Cancer
• Stomach Neoplasms

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	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
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	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan
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	Atlanta	Georgia
United States	Research Site	Baltimore	Maryland
United States	Research Site	Boston	Massachusetts
United States	Research Site	Charlottesville	Virginia
United States	Research Site	Duarte	California
United States	Research Site	Kansas City	Missouri
United States	Research Site	Marietta	Georgia
United States	Research Site	Mineola	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
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
Vietnam	Research Site	Hanoi
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,  Italy,  Japan,  Poland,  Spain,  Switzerland,  Taiwan,  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.