An Open Label Study Evaluating the Efficacy and Safety of Etrumadenant (AB928) Based Treatment Combinations in Participants With Metastatic Colorectal Cancer.

NCT ID: NCT04660812

Last Updated: 2025-10-20

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

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

227 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-10

Study Completion Date

2025-09-05

Brief Summary

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This randomized phase 1b/2 open-label study will evaluate the antitumour activity and safety of etrumadenant (AB928) treatment combinations in participants with metastatic colorectal cancer.

Detailed Description

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This is a multicenter, open-label Phase 1b/2 study in participants with metastatic colorectal cancer that will assess the antitumour activity and safety of etrumadenant.

Approximately 250 participants will be enrolled to 1 of 3 cohorts:

Cohort A) etrumadenant + zimberelimab +mFOLFOX-6 +/-bevacizumab vs mFOLFOX-6 +/-bevacizumab

Cohort B) etrumadenant + zimberelimab +mFOLFOX-6 +/-bevacizumab vs regorafenib

Cohort C) chemotherapy-free combinations of etrumadenant + zimberelimab + other agents

The primary objective of this clinical study is to evaluate the safety of etrumadenant-based combination therapy in participants with metastatic colorectal cancer.

Conditions

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Metastatic Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Etrumadenant + Zimberelimab + mFOLFOX-6 +/- Bevacizumab

Participants will receive oral etrumadenant in combination with zimberelimab +mFOLFOX-6 +/-bevacizumab by IV infusion.

Group Type EXPERIMENTAL

Etrumadenant

Intervention Type DRUG

Etrumadenant is a dual adenosine receptor (A2aR and A2bR) antagonist

Zimberelimab

Intervention Type DRUG

Zimberelimab is a fully human anti-PD-1 monoclonal antibody

Bevacizumab

Intervention Type DRUG

Bevacizumab is administered as part of standard chemotherapy regimen

m-FOLFOX-6 regimen

Intervention Type DRUG

mFOLFOX-6 regimen is administered as part of standard chemotherapy regimen

mFOLFOX-6 +/- Bevacizumab

Participants will receive mFOLFOX-6 +/- bevacizumab by IV infusion.

Group Type ACTIVE_COMPARATOR

Bevacizumab

Intervention Type DRUG

Bevacizumab is administered as part of standard chemotherapy regimen

m-FOLFOX-6 regimen

Intervention Type DRUG

mFOLFOX-6 regimen is administered as part of standard chemotherapy regimen

Regorafenib

Participants will receive oral regorafenib

Group Type ACTIVE_COMPARATOR

Regorafenib

Intervention Type DRUG

Regorafenib is administered as part of standard chemotherapy regimen

AB680 + Etrumadenant + Zimberelimab

Participants will receive oral etrumadenant in combination with AB680 + zimberelimab by IV infusion.

Group Type EXPERIMENTAL

AB680

Intervention Type DRUG

AB680 is a cluster of differentiated CD73 Inhibitor

Etrumadenant

Intervention Type DRUG

Etrumadenant is a dual adenosine receptor (A2aR and A2bR) antagonist

Zimberelimab

Intervention Type DRUG

Zimberelimab is a fully human anti-PD-1 monoclonal antibody

Interventions

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AB680

AB680 is a cluster of differentiated CD73 Inhibitor

Intervention Type DRUG

Etrumadenant

Etrumadenant is a dual adenosine receptor (A2aR and A2bR) antagonist

Intervention Type DRUG

Zimberelimab

Zimberelimab is a fully human anti-PD-1 monoclonal antibody

Intervention Type DRUG

Bevacizumab

Bevacizumab is administered as part of standard chemotherapy regimen

Intervention Type DRUG

m-FOLFOX-6 regimen

mFOLFOX-6 regimen is administered as part of standard chemotherapy regimen

Intervention Type DRUG

Regorafenib

Regorafenib is administered as part of standard chemotherapy regimen

Intervention Type DRUG

Other Intervention Names

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AB928 AB122

Eligibility Criteria

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Inclusion Criteria

* Male and female participants ≥ 18 years of age
* Histologically confirmed metastatic colorectal adenocarcinoma
* Must have at least 1 measurable lesion per RECIST v1.1
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy at least 3 months
* Adequate hematologic and end-organ function
* Negative HIV, Hep B and Hep C antibody testing
* Agreement to remain abstinent or use contraceptive measures with female partners of reproductive potential, and agreement to refrain from donating sperm, for 30 days after the last dose of etrumadenant, 90 days after the last dose of zim, 180 days after mFOLFOX-6 and 180 days after bev, whichever is longer.

* Disease progression following not more than one prior line of treatment for mCRC that consisted of oxaliplatin or irinotecan containing chemotherapy in combination with a biologic agent

* Disease progression during or following not more than two separate lines of treatment for mCRC that consisted of oxaliplatin, and irinotecan containing chemotherapy in combination with a biologic agent

Exclusion Criteria

* Previous anticancer treatment within 4 weeks prior to initiation of study treatment
* Prior allogeneic stem cell or solid organ transplant
* Treatment with systemic immunostimulatory agents within 4 weeks prior to initiation of study treatment
* Use of any live vaccines against infectious diseases within 28 days of first dose.
* Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
* Current treatment with anti-viral therapy for HBV
* Structurally unstable bone lesions suggesting impending fracture
* History or leptomeningeal disease
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
* History of malignancy other than colorectal cancer within 2 years prior to screening, except for malignancies such as non-melanoma skin carcinoma or ductal carcinoma in situ
* Active tuberculosis
* Treatment with therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to initiating study treatment
* Severe infection within 4 weeks (28 days) prior to initiation of study treatment
* Significant cardiovascular disease, unstable or new onset of angina within 3 months prior to initiation of treatment, or myocardial infarction within 6 months prior to study treatment or unstable arrhythmia
* Major surgical procedures, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for major surgical procedure during the study
* Known allergy or hypersensitivity to any of the study drugs or their excipients
* Inability to swallow medications
* Malabsorption condition that would alter the absorption of orally administered medications
* Evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e., in the absence of therapeutic anticoagulation)
* Prior treatment with an agent targeting the adenosine pathway
* Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain Barré syndrome, or multiple sclerosis

* Prior treatment with immune checkpoint blockade therapies including anti-cytotoxic T lymphocyte-associated protein-4, anti PD-1, and anti-PD-L1 therapeutic antibodies
* Mutation in the BRAF oncogene. Patients with unknown BRAF status will be required to undergo testing at a local laboratory and provide results at screening
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role collaborator

Arcus Biosciences, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Arcus Biosciences

Locations

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Arizona Clinical Research Center Inc

Tucson, Arizona, United States

Site Status

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

UCLA Hematology Oncology

Santa Monica, California, United States

Site Status

Yale Cancer Center

New Haven, Connecticut, United States

Site Status

Sibley Memorial Hospital

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

Site Status

Winship Cancer Institute at Emory University

Atlanta, Georgia, United States

Site Status

Ochsner Medical Center (OMC)

New Orleans, Louisiana, United States

Site Status

American Oncology Partners of Maryland PA

Bethesda, Maryland, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Comprehensive Cancer Centers Of Nevada

Las Vegas, Nevada, United States

Site Status

NYU Langone Medical Center - NYU Medical Oncology Associates

New York, New York, United States

Site Status

New York-Presbyterian Hospital-Columbia University Medical Center

New York, New York, United States

Site Status

Prisma Health-Upstate

Greenville, South Carolina, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

University of Wisconsin School of Medicine

Madison, Wisconsin, United States

Site Status

Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest

Bordeaux, , France

Site Status

Centre Georges Francois Leclerc

Dijon, , France

Site Status

Hopital Hotel Dieu

Nantes, , France

Site Status

Hopital Saint Antoine

Paris, , France

Site Status

Groupe Hospitalier Pitie-Salpetriere-Centre De Recherche et de Medecine de l'Obesite

Paris, , France

Site Status

CHU la Miletrie

Poitiers, , France

Site Status

IRCCS - Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis

Castellana Grotte, , Italy

Site Status

Azienda Ospedaliero Universitaria Careggi-S.O.D. Patologia Medica

Florence, , Italy

Site Status

Azienda Ospedaliera Niguarda Ca' Granda

Milan, , Italy

Site Status

Instituto Europeo di Oncologia

Milan, , Italy

Site Status

Istituto Clinico Humanitas IRCCS

Rozzano, , Italy

Site Status

Universita di Siena - Azienda Ospedaliera Universitaria Senese-Policlincio Santa Maria Alle Scotte

Siena, , Italy

Site Status

Chonnam National University Hwasun Hospital

Hwasun, , South Korea

Site Status

Seoul National University Bundang Hospital

Seoul, , South Korea

Site Status

Seoul National University Hospital (SNUH)

Seoul, , South Korea

Site Status

Severance Hospital | Yonsei University Health System

Seoul, , South Korea

Site Status

Asan Medical Center | University of Ulsan College of Medicine

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Korea University Anam Hospital

Seoul, , South Korea

Site Status

Kyungpook National University Chilgok Hospital

Seoul, , South Korea

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Site Status

Complejo Hospitalario de Orense

Ourense, , Spain

Site Status

Clinica Universidad Navarra-Sede Madrid

Pamplona, , Spain

Site Status

Corporacio Sanitaria Parc Tauli

Sabadell, , Spain

Site Status

Belfast City Hospital

Belfast, Northern Ireland, United Kingdom

Site Status

Aberdeen Royal Infirmary

Aberdeen, Scotland, United Kingdom

Site Status

Countries

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United States France Italy South Korea Spain United Kingdom

Related Links

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Other Identifiers

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2020-005386-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ARC-9

Identifier Type: -

Identifier Source: org_study_id

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