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

NCT04660812 | Completed Phase 1 FDA Drug

• 2 other identifiers: ARC-92020-005386-13
• Study Type: interventional
• Target: 227
• Locations: 6 countries
• Sites: 44

Brief Summary

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.

Conditions

Metastatic Colorectal Cancer

Keywords

mCRC

Outcome Measures

Primary Outcomes (3)

• Cohort A and B - Progression-free Survival (PFS)

  PFS according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by the Investigator

  From randomization until death from any cause (up to approximately 3-7 years)

• Cohort C - Objective Response Rate (ORR)

  ORR according to RECIST v1.1, as assessed by the Investigator

  From randomization until death from any cause (up to approximately 3-7 years)

• Number of Participants With Treatment-emergent Adverse Events

  Up to approximately 10 Months

Secondary Outcomes (14)

• Cohorts A and B - Objective Response Rate (ORR)

  From randomization until death from any cause (up to approximately 3-7 years)

• Cohorts A, B, and C- Duration of Disease Response (DoR)

  From randomization until death from any cause (up to approximately 3-7 years)

• Cohorts A, B, and C- Disease Control Rate (DCR)

  From randomization until death from any cause (up to approximately 3-7 years)

• Cohorts A and B - Overall Survival (OS)

  From randomization until death from any cause (up to approximately 3-7 years)

• Observed Maximum Concentration (Cmax) of Etrumadenant and its Metabolites

  From randomization until death from any cause (up to approximately 10 months)

Study Arms (4)

Etrumadenant + Zimberelimab + mFOLFOX-6 +/- Bevacizumab

EXPERIMENTAL

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

Drug: Etrumadenant; Drug: Zimberelimab; Drug: Bevacizumab; Drug: m-FOLFOX-6 regimen

mFOLFOX-6 +/- Bevacizumab

ACTIVE COMPARATOR

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

Drug: Bevacizumab; Drug: m-FOLFOX-6 regimen

Regorafenib

ACTIVE COMPARATOR

Participants will receive oral regorafenib

Drug: Regorafenib

AB680 + Etrumadenant + Zimberelimab

EXPERIMENTAL

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

Drug: AB680; Drug: Etrumadenant; Drug: Zimberelimab

Interventions

AB680 DRUG

AB680 is a cluster of differentiated CD73 Inhibitor

AB680 + Etrumadenant + Zimberelimab

Etrumadenant DRUG

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

Also known as: AB928

AB680 + Etrumadenant + Zimberelimab; Etrumadenant + Zimberelimab + mFOLFOX-6 +/- Bevacizumab

Zimberelimab DRUG

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

Also known as: AB122

AB680 + Etrumadenant + Zimberelimab; Etrumadenant + Zimberelimab + mFOLFOX-6 +/- Bevacizumab

Bevacizumab DRUG

Bevacizumab is administered as part of standard chemotherapy regimen

Etrumadenant + Zimberelimab + mFOLFOX-6 +/- Bevacizumab; mFOLFOX-6 +/- Bevacizumab

m-FOLFOX-6 regimen DRUG

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

Etrumadenant + Zimberelimab + mFOLFOX-6 +/- Bevacizumab; mFOLFOX-6 +/- Bevacizumab

Regorafenib DRUG

Regorafenib is administered as part of standard chemotherapy regimen

Regorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Arcus Biosciences, Inc.: lead
• Gilead Sciences: collaborator

Study Sites (44)

Arizona Clinical Research Center Inc

Tucson, Arizona, 85715, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

UCLA Hematology Oncology

Santa Monica, California, 90404, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016-2633, United States

Location

Winship Cancer Institute at Emory University

Atlanta, Georgia, 30322, United States

Location

Ochsner Medical Center (OMC)

New Orleans, Louisiana, 70121, United States

Location

American Oncology Partners of Maryland PA

Bethesda, Maryland, 20817, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Comprehensive Cancer Centers Of Nevada

Las Vegas, Nevada, 89169, United States

Location

NYU Langone Medical Center - NYU Medical Oncology Associates

New York, New York, 10016, United States

Location

New York-Presbyterian Hospital-Columbia University Medical Center

New York, New York, 10032, United States

Location

Prisma Health-Upstate

Greenville, South Carolina, 29605, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37203, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37232, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Wisconsin School of Medicine

Madison, Wisconsin, 53792, United States

Location

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

Bordeaux, 33076, France

Location

Centre Georges Francois Leclerc

Dijon, 21000, France

Location

Hopital Hotel Dieu

Nantes, 44093, France

Location

Hopital Saint Antoine

Paris, 75012, France

Location

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

Paris, 75651, France

Location

CHU la Miletrie

Poitiers, 86000, France

Location

IRCCS - Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis

Castellana Grotte, 70013, Italy

Location

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

Florence, 50134, Italy

Location

Azienda Ospedaliera Niguarda Ca' Granda

Milan, 20141, Italy

Location

Instituto Europeo di Oncologia

Milan, 20162, Italy

Location

Istituto Clinico Humanitas IRCCS

Rozzano, 20089, Italy

Location

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

Siena, 53100, Italy

Location

Chonnam National University Hwasun Hospital

Hwasun, 58128, South Korea

Location

Seoul National University Bundang Hospital

Seoul, 13620, South Korea

Location

Seoul National University Hospital (SNUH)

Seoul, 3080, South Korea

Location

Severance Hospital | Yonsei University Health System

Seoul, 3722, South Korea

Location

Asan Medical Center | University of Ulsan College of Medicine

Seoul, 5538, South Korea

Location

Samsung Medical Center

Seoul, 6351, South Korea

Location

Korea University Anam Hospital

Seoul, 8241, South Korea

Location

Kyungpook National University Chilgok Hospital

Seoul, South Korea

Location

Hospital Universitario La Paz

Madrid, 28007, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28046, Spain

Location

Complejo Hospitalario de Orense

Ourense, 32005, Spain

Location

Clinica Universidad Navarra-Sede Madrid

Pamplona, 31008, Spain

Location

Corporacio Sanitaria Parc Tauli

Sabadell, 8208, Spain

Location

Belfast City Hospital

Belfast, Northern Ireland, BT9 7AB, United Kingdom

Location

Aberdeen Royal Infirmary

Aberdeen, Scotland, AB25 2ZN, United Kingdom

Location

Related Links

• ARC-9 - Public website

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

quemliclustat; zimberelimab; Bevacizumab; regorafenib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Medical Director

  Arcus Biosciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2020
• First Posted: December 9, 2020
• Study Start: May 10, 2021
• Primary Completion: September 5, 2025
• Study Completion: September 5, 2025
• Last Updated: October 20, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

ES (5); IT (6); GB (2); FR (6); KR (8); US (17)