NCT06346392

Brief 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.

Trial Health

88
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
572

participants targeted

Target at P50-P75 for phase_3 gastric-cancer

Timeline
5mo left

Started Mar 2024

Shorter than P25 for phase_3 gastric-cancer

Geographic Reach
19 countries

186 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress86%
Mar 2024Sep 2026

First Submitted

Initial submission to the registry

February 28, 2024

Completed
5 days until next milestone

Study Start

First participant enrolled

March 4, 2024

Completed
1 month until next milestone

First Posted

Study publicly available on registry

April 4, 2024

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 14, 2026

Expected
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 14, 2026

Last Updated

March 9, 2026

Status Verified

March 1, 2026

Enrollment Period

2.2 years

First QC Date

February 28, 2024

Last Update Submit

March 6, 2026

Conditions

Keywords

Gastric cancerGastroesophageal junction cancerPhase IIIClaudin 18.2AZD0901

Outcome Measures

Primary Outcomes (2)

  • 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).

  • 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 Outcomes (12)

  • OS in all randomized participants

    From date of first dose/randomisation until the date of death due to any cause (approximately 3 years).

  • PFS for 3L+ participants

    From date of first dose/randomisation until disease progression or death in the absence of progression (approximately 3 years).

  • Objective Response Rate (ORR) in all randomized participants

    From date of first dose of AZD0901 up until progression, or the last evaluable assessment in the absence of progression (approximately 3 years).

  • ORR for 3L+ participants

    From date of first dose of AZD0901 up until progression, or the last evaluable assessment in the absence of progression (approximately 3 years).

  • Duration of Response (DoR) in all randomized participants

    From the date of first documented confirmed response until date of documented progression (approximately 3 years).

  • +7 more secondary outcomes

Study Arms (3)

AZD0901 arm 1

EXPERIMENTAL

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

Drug: AZD0901

AZD0901 Arm 2

EXPERIMENTAL

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

Drug: AZD0901

Investigator's choice arm

ACTIVE COMPARATOR

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

Drug: Ramucirumab+ paclitaxelDrug: PaclitaxelDrug: DocetaxelDrug: IrinotecanDrug: TAS-102Drug: Apatinib

Interventions

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

Investigator's choice arm

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

Investigator's choice arm

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

Investigator's choice arm

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)

Investigator's choice arm

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

Investigator's choice arm

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

Also known as: Sonesitatug Vedotin
AZD0901 arm 1

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

Investigator's choice arm

Eligibility Criteria

Age18 Years - 130 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Capable of giving signed informed consent prior to any study procedure.
  • 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.
  • 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.
  • 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.
  • Must have at least one measurable or evaluable lesion assessed by the Investigator based on RECIST 1.1.
  • ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
  • Predicted life expectancy of ≥ 12 weeks.
  • Adequate organ and bone marrow function
  • Body weight of ≥ 35 kg.
  • Sex and Contraceptive Requirements

You may not qualify if:

  • 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.
  • Participant has significant or unstable gastric bleeding and/or untreated gastric ulcers.
  • 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.
  • Participant has known clinically significant corneal disease (eg, active keratitis or corneal ulcerations).
  • 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).
  • 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).
  • History of thromboembolic events:
  • 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
  • History of arterial thromboembolism within the past 12 months prior to randomization
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (186)

Research Site

Birmingham, Alabama, 35233, United States

WITHDRAWN

Research Site

Mobile, Alabama, 36604, United States

ACTIVE NOT RECRUITING

Research Site

Tucson, Arizona, 85719, United States

ACTIVE NOT RECRUITING

Research Site

Duarte, California, 91010, United States

ACTIVE NOT RECRUITING

Research Site

Fullerton, California, 92835, United States

WITHDRAWN

Research Site

Irvine, California, 92618, United States

ACTIVE NOT RECRUITING

Research Site

Los Angeles, California, 90048, United States

ACTIVE NOT RECRUITING

Research Site

Los Angeles, California, 90089, United States

ACTIVE NOT RECRUITING

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Newport Beach, California, 92663, United States

RECRUITING

Research Site

Santa Rosa, California, 95403, United States

WITHDRAWN

Research Site

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

ACTIVE NOT RECRUITING

Research Site

Fleming Island, Florida, 32003, United States

WITHDRAWN

Research Site

Hollywood, Florida, 33021, United States

ACTIVE NOT RECRUITING

Research Site

Orlando, Florida, 32804, United States

ACTIVE NOT RECRUITING

Research Site

Atlanta, Georgia, 30322, United States

WITHDRAWN

Research Site

Marietta, Georgia, 30060, United States

ACTIVE NOT RECRUITING

Research Site

Honolulu, Hawaii, 96819, United States

WITHDRAWN

Research Site

Boise, Idaho, 83712, United States

ACTIVE NOT RECRUITING

Research Site

Lexington, Kentucky, 40536, United States

ACTIVE NOT RECRUITING

Research Site

Baltimore, Maryland, 21287, United States

WITHDRAWN

Research Site

Boston, Massachusetts, 02114, United States

ACTIVE NOT RECRUITING

Research Site

Ann Arbor, Michigan, 48106, United States

ACTIVE NOT RECRUITING

Research Site

Ann Arbor, Michigan, 48109, United States

ACTIVE NOT RECRUITING

Research Site

Kansas City, Missouri, 64111, United States

ACTIVE NOT RECRUITING

Research Site

St Louis, Missouri, 63110, United States

WITHDRAWN

Research Site

St Louis, Missouri, 63128, United States

WITHDRAWN

Research Site

Mineola, New York, 11501, United States

ACTIVE NOT RECRUITING

Research Site

New York, New York, 10016, United States

ACTIVE NOT RECRUITING

Research Site

New York, New York, 10032, United States

ACTIVE NOT RECRUITING

Research Site

New York, New York, 10065, United States

RECRUITING

Research Site

Cincinnati, Ohio, 45219, United States

WITHDRAWN

Research Site

Portland, Oregon, 97239, United States

WITHDRAWN

Research Site

Philadelphia, Pennsylvania, 19111, United States

ACTIVE NOT RECRUITING

Research Site

York, Pennsylvania, 17403, United States

ACTIVE NOT RECRUITING

Research Site

Charlottesville, Virginia, 22908, United States

ACTIVE NOT RECRUITING

Research Site

Fredericksburg, Virginia, 22408, United States

ACTIVE NOT RECRUITING

Research Site

Olympia, Washington, 98502, United States

ACTIVE NOT RECRUITING

Research Site

Seattle, Washington, 98109, United States

WITHDRAWN

Research Site

Porto Alegre, 91350-200, Brazil

RECRUITING

Research Site

Ribeirão Preto, 14051-140, Brazil

RECRUITING

Research Site

São Paulo, 05652-900, Brazil

RECRUITING

Research Site

Vitória, 29043-272, Brazil

RECRUITING

Research Site

Calgary, Alberta, T2N 4N2, Canada

WITHDRAWN

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Barrie, Ontario, L4M 6M2, Canada

RECRUITING

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London, Ontario, N6C 2R5, Canada

RECRUITING

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North York, Ontario, M2K 1E1, Canada

RECRUITING

Research Site

Ottawa, Ontario, K1H 8L6, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Research Site

Montreal, Quebec, H3G 1A4, Canada

RECRUITING

Research Site

Montreal, Quebec, H3T 1E2, Canada

WITHDRAWN

Research Site

Beijing, 100210, China

RECRUITING

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Changchun, 130021, China

RECRUITING

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Changsha, 410013, China

WITHDRAWN

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Chengdu, 610000, China

RECRUITING

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Chengdu, 610042, China

RECRUITING

Research Site

Fuzhou, 350001, China

RECRUITING

Research Site

Fuzhou, 350014, China

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Guangzhou, 510060, China

RECRUITING

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Guangzhou, 510120, China

RECRUITING

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Guangzhou, 510655, China

RECRUITING

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Guangzhou, 510700, China

RECRUITING

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Hangzhou, 310020, China

RECRUITING

Research Site

Hangzhou, 310022, China

RECRUITING

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Harbin, 150049, China

RECRUITING

Research Site

Hefei, 230022, China

RECRUITING

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Hefei, 230031, China

RECRUITING

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Hefei, 230601, China

RECRUITING

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Jinan, 250117, China

RECRUITING

Research Site

Jining, 272029, China

RECRUITING

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Lanzhou, 730000, China

RECRUITING

Research Site

Lishui, 323000, China

RECRUITING

Research Site

Luoyang, 471003, China

WITHDRAWN

Research Site

Nanjing, 210008, China

RECRUITING

Research Site

Nanjing, 210009, China

WITHDRAWN

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Qingdao, 266003, China

RECRUITING

Research Site

Shanghai, 200025, China

RECRUITING

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Shanghai, 200032, China

RECRUITING

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Shanghai, 200040, China

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Shenyang, 110042, China

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Shijiazhuang, 050011, China

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Research Site

Suzhou, 215004, China

RECRUITING

Research Site

Tianjin, 300060, China

RECRUITING

Research Site

Ürümqi, 830000, China

SUSPENDED

Research Site

Wuhan, 430000, China

RECRUITING

Research Site

Wuhan, 430030, China

RECRUITING

Research Site

Xi'an, 710061, China

RECRUITING

Research Site

Yinchuan, 750004, China

RECRUITING

Research Site

Zhengzhou, 450003, China

RECRUITING

Research Site

Besançon, 25030, France

RECRUITING

Research Site

Brest, 29200, France

ACTIVE NOT RECRUITING

Research Site

Lille, 59037, France

RECRUITING

Research Site

Lyon, 69008, France

ACTIVE NOT RECRUITING

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Nantes, 44000, France

RECRUITING

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Paris, 75571, France

RECRUITING

Research Site

Poitiers, 86021, France

RECRUITING

Research Site

Berlin, 10249, Germany

RECRUITING

Research Site

Berlin, 13353, Germany

RECRUITING

Research Site

Dresden, 01067, Germany

WITHDRAWN

Research Site

Dresden, 01370, Germany

WITHDRAWN

Research Site

Essen, 45136, Germany

WITHDRAWN

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Frankfurt, 60488, Germany

RECRUITING

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Göttingen, 37075, Germany

RECRUITING

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Hamburg, 20246, Germany

RECRUITING

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Heidelberg, 69120, Germany

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Heilbronn, 74078, Germany

RECRUITING

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Leipzig, 04103, Germany

RECRUITING

Research Site

Mainz, 55131, Germany

WITHDRAWN

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Marburg, 35043, Germany

RECRUITING

Research Site

Moers, 47441, Germany

RECRUITING

Research Site

München, 81377, Germany

RECRUITING

Research Site

Hong Kong, 150001, Hong Kong

RECRUITING

Research Site

Hong Kong, Hong Kong

RECRUITING

Research Site

Ahmedabad, 380015, India

RECRUITING

Research Site

Bengaluru, 560027, India

WITHDRAWN

Research Site

Hyderabad, 500032, India

RECRUITING

Research Site

Mumbai, 400012, India

RECRUITING

Research Site

New Delhi, 110085, India

RECRUITING

Research Site

Florence, 50134, Italy

RECRUITING

Research Site

Milan, 20133, Italy

RECRUITING

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Milan, 20162, Italy

RECRUITING

Research Site

Modena, 41124, Italy

WITHDRAWN

Research Site

Naples, 80131, Italy

RECRUITING

Research Site

Padua, 35128, Italy

RECRUITING

Research Site

Pisa, 56100, Italy

RECRUITING

Research Site

Vicenza, 36100, Italy

RECRUITING

Research Site

Fukuoka, 812-8582, Japan

RECRUITING

Research Site

Kashiwa, 227-8577, Japan

RECRUITING

Research Site

Kōtoku, 135-8550, Japan

RECRUITING

Research Site

Nagoya, 464-8681, Japan

RECRUITING

Research Site

Ogaki-shi, 503-8502, Japan

RECRUITING

Research Site

Osaka, 541-8567, Japan

RECRUITING

Research Site

Sunto-gun, 411-8777, Japan

RECRUITING

Research Site

Tokyo, 104-0045, Japan

RECRUITING

Research Site

Toyoake-shi, 470-1192, Japan

RECRUITING

Research Site

Yokohama, 241-8515, Japan

RECRUITING

Research Site

Bielsko-Biala, 43-300, Poland

RECRUITING

Research Site

Gdansk, 80-219, Poland

RECRUITING

Research Site

Katowice, 40-514, Poland

ACTIVE NOT RECRUITING

Research Site

Krakow, 31-501, Poland

RECRUITING

Research Site

Lublin, 20-080, Poland

RECRUITING

Research Site

Szczecin, 71-730, Poland

WITHDRAWN

Research Site

Słupsk, 76-200, Poland

ACTIVE NOT RECRUITING

Research Site

Tomaszów Mazowiecki, 97-200, Poland

WITHDRAWN

Research Site

Warsaw, 02-034, Poland

RECRUITING

Research Site

Warsaw, 04-141, Poland

RECRUITING

Research Site

Gyeonggi-do, 13620, South Korea

RECRUITING

Research Site

Seoul, 03080, South Korea

RECRUITING

Research Site

Seoul, 03722, South Korea

RECRUITING

Research Site

Seoul, 05505, South Korea

ACTIVE NOT RECRUITING

Research Site

Seoul, 06351, South Korea

RECRUITING

Research Site

Seoul, 06591, South Korea

RECRUITING

Research Site

Barcelona, 08036, Spain

RECRUITING

Research Site

Barcelona, 8035, Spain

RECRUITING

Research Site

Madrid, 28034, Spain

RECRUITING

Research Site

Madrid, 28041, Spain

RECRUITING

Research Site

Ourense, 32005, Spain

RECRUITING

Research Site

Santander, 39008, Spain

RECRUITING

Research Site

Seville, 41013, Spain

RECRUITING

Research Site

Bern, 3010, Switzerland

ACTIVE NOT RECRUITING

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Geneva, 1205, Switzerland

ACTIVE NOT RECRUITING

Research Site

Lausanne, 1011, Switzerland

ACTIVE NOT RECRUITING

Research Site

Zurich, 8032, Switzerland

ACTIVE NOT RECRUITING

Research Site

Kaohsiung City, 00807, Taiwan

RECRUITING

Research Site

Kaohsiung City, 83301, Taiwan

RECRUITING

Research Site

Taichung, 40447, Taiwan

RECRUITING

Research Site

Tainan, 704, Taiwan

RECRUITING

Research Site

Taipei, 10002, Taiwan

RECRUITING

Research Site

Taipei, 112, Taiwan

RECRUITING

Research Site

Taoyuan District, 333, Taiwan

RECRUITING

Research Site

Bangkok, 10700, Thailand

ACTIVE NOT RECRUITING

Research Site

Dusit, 10300, Thailand

ACTIVE NOT RECRUITING

Research Site

Hat Yai, 90110, Thailand

ACTIVE NOT RECRUITING

Research Site

Khon Kaen, 40002, Thailand

ACTIVE NOT RECRUITING

Research Site

Ankara, 06230, Turkey (Türkiye)

RECRUITING

Research Site

Diyarbakır, 21280, Turkey (Türkiye)

RECRUITING

Research Site

Erzurum, 25240, Turkey (Türkiye)

RECRUITING

Research Site

Istanbul, 34098, Turkey (Türkiye)

RECRUITING

Research Site

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

Research Site

London, EC1A 7BE, United Kingdom

RECRUITING

Research Site

London, SW3 6JJ, United Kingdom

RECRUITING

Research Site

Manchester, M20 4BX, United Kingdom

RECRUITING

Research Site

Oxford, OX3 7LE, United Kingdom

RECRUITING

Research Site

Taunton, TA1 5DA, United Kingdom

RECRUITING

Research Site

Hanoi, 100000, Vietnam

RECRUITING

Research Site

Ho Chi Minh City, 700000, Vietnam

RECRUITING

Research Site

Vinh, 460000, Vietnam

RECRUITING

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

PaclitaxelDocetaxelIrinotecantrifluridine tipiracil drug combinationapatinib

Condition Hierarchy (Ancestors)

Gastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesStomach Diseases

Intervention Hierarchy (Ancestors)

TaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenesCamptothecinAlkaloidsHeterocyclic Compounds

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Masking Details
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.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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)
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 28, 2024

First Posted

April 4, 2024

Study Start

March 4, 2024

Primary Completion (Estimated)

May 14, 2026

Study Completion (Estimated)

September 14, 2026

Last Updated

March 9, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will share

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Access Criteria
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
More information

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