An Open Label Study Evaluating the Efficacy and Safety of Etrumadenant (AB928) Based Treatment Combinations in Participants With Metastatic Colorectal Cancer. (ARC-9)

A Phase 1b/2, Open-Label, Randomized Platform Study Evaluating The Efficacy and Safety of AB928 Based Treatment Combinations in Patients With Metastatic Colorectal Cancer

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: AB680; Drug: Etrumadenant; Drug: Zimberelimab; Drug: Bevacizumab; Drug: m-FOLFOX-6 regimen; Drug: Regorafenib

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 227
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
  • Dijon, France, 21000
    • Centre GEORGES FRANÇOIS LECLERC
  • Nantes Cedex 1, France, 44093
    • Hôpital Hotel Dieu
  • Paris, France, 75012
    • Hôpital Saint Antoine
  • Paris Cedex 13, France, 75651
    • Groupe Hospitalier Pitie-Salpetriere-Centre De Recherche et de Medecine de l'Obesite
  • Poitiers, France, 86000
    • Chu La Miletrie
• Italy
  • Castellana Grotte, Italy, 70013
    • IRCCS - Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis
  • Firenze, Italy
    • U.O Farmeaceutica Ospealiera e Politche del Farmaco
  • Milano, Italy, 20141
    • Instituto Europeo di Oncologia
  • Milano, Italy, 20162
    • Azienda Ospedaliera Niguarda Ca' Granda
  • Rozzano, Italy, 20089
    • Istituto Clinico Humanitas IRCCS
  • Siena, Italy, 53100
    • Universita di Siena - Azienda Ospedaliera Universitaria Senese-Policlincio Santa Maria Alle Scotte
• Korea, Republic of
  • Seoul, Korea, Republic of, 6351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 3722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 3080
    • Seoul National University Hospital (SNUH)
  • Seoul, Korea, Republic of, 5538
    • Asan Medical Center, University of Ulsan College of Medicine
  • Seoul, Korea, Republic of, 8241
    • Korea University Anam Hospital
• Spain
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Orense, Spain, 32005
    • Complejo Hospitalario de Orense
• United Kingdom
  • Scotland
    • Aberdeen, Scotland, United Kingdom, AB25 2ZN
      • Aberdeen Royal Infirmary
• United States
  • Arizona
    • Tucson, Arizona, United States, 85715
      • Arizona Clinical Research Center, Inc
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Santa Monica, California, United States, 90404
      • UCLA Hematology Oncology
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20016-2633
      • Sibley Memorial Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute at Emory University
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center (OMC)
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • American Oncology Partners of Maryland,PA
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Medical Center - NYU Medical Oncology Associates
    • New York, New York, United States, 10032
      • New York-Presbyterian Hospital-Columbia University Medical Center
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Prisma Health-Upstate
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

  • Inclusion Criteria for Cohort A:

• 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

  • Inclusion Criteria for Cohort B:
• Disease progression during or following not more that 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

  • Exclusion Criteria for Cohorts A and B:
• Prior treatment with immune checkpoint blockade therapies including anit-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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Etrumadenant + Zimberelimab + mFOLFOX-6 +/- Bevacizumab; Participants will receive oral etrumadenant in combination with zimberelimab +mFOLFOX-6 +/-bevacizumab by IV infusion.	Drug: Etrumadenant; Etrumadenant is a dual adenosine receptor (A2aR and A2bR) antagonist; Other Names: AB928; Drug: Zimberelimab; Zimberelimab is a fully human anti-PD-1 monoclononal antibody; Other Names: AB122; Drug: Bevacizumab; Bevacizumab is administered as part of standard chemotherapy regimen; Drug: m-FOLFOX-6 regimen; mFOLFOX-6 regimen is administered as part of standard chemotherapy regimen
Active Comparator: mFOLFOX-6 +/- Bevacizumab; Participants will receive mFOLFOX-6 +/- bevacizumab by IV infusion.	Drug: Bevacizumab; Bevacizumab is administered as part of standard chemotherapy regimen; Drug: m-FOLFOX-6 regimen; mFOLFOX-6 regimen is administered as part of standard chemotherapy regimen
Active Comparator: Regorafenib; Participants will receive oral regorafenib	Drug: Regorafenib; Regorafenib is adminstered as part of standard chemotherapy regimen
Experimental: AB680 + Etrumadent+ Zimberelimab; Participants will receive oral etrmadenant in combination with AB680 + zimberelimab by IV infusion.	Drug: AB680; AB680 is a cluster of differentiated CD73 Inhibitor; Drug: Etrumadenant; Etrumadenant is a dual adenosine receptor (A2aR and A2bR) antagonist; Other Names: AB928; Drug: Zimberelimab; Zimberelimab is a fully human anti-PD-1 monoclononal antibody; Other Names: AB122

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohorts A and B - 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)
Cohorts A, B, and C- Duration of Disease Response (DoR)	DoR according to RECIST v1.1, as assessed by the Investigator	From randomization until death from any cause (up to approximately 3-7 years)
Cohorts A, B, and C- Disease Control Rate (DCR)	DCR according to RECIST v1.1, as assessed by the Investigator	From randomization until death from any cause (up to approximately 3-7 years)
Cohorts A and B - Overall Survival (OS)	OS according to RECIST v1.1, as assessed by the Investigator	From randomization until death from any cause (up to approximately 3-7 years)
Observed Maximum Concentration (Cmax) of Etrumadenant and its Metabolites	Cycle 1 Day 1 and Cycle 2 Day 1	From randomization until death from any cause (up to approximately 10 months)
Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours [AUC(0-24)] of Etrumadenant and its Metabolites		Up to 24 hours following Day 1 Cycle 1 and Cycle 2 (each cycle is 28 days)
Trough Concentrations of Etrumadenant and its Metabolites		Multiple timepoints up to approximately 16 months
Cmax End of Infusion (EOI) of AB680		At the end of infusion on Day 1 Cycle 1 and Cycle 2 (each cycle is 28 days)
Area Under the Plasma Concentration Versus Time Curve From Time Zero to 336 Hours [AUC(0-336)] of AB680		Up to 336 hours following Day 1 Cycle and Cycle 2 (each cycle is 28 days)]
Trough Concentrations of AB680		Multiple timepoints up to approximately 16 months
Cmax EOI of Zimberelimab		Multiple timepoints up to approximately 16 months
AUV(0-336) of Zimberelimab		Cycle 1 Day 1 up to 336 hours
Trough Concentrations of Zimberelimab		Multiple timepoints up to approximately 16 months
Number of Participants With Anti-Drug Antibodies to the Biologic Component(s) of Combination Therapy		Up to approximately 10 months

Collaborators and Investigators

• Sponsor: Arcus Biosciences, Inc.
• Collaborators: Gilead Sciences
• Investigators: Study Director: Medical Director, Arcus Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2021
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: December 3, 2020
• First Submitted That Met QC Criteria: December 3, 2020
• First Posted (Actual): December 9, 2020

Study Record Updates

• Last Update Posted (Estimated): February 6, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: mCRC
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: ARC-9; 2020-005386-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Arcus will provide access to individual de-identified participant data and related study documents (e.g., protocol, Statistical Analysis Plan [SAP], Clinical Study Report [CSR]) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions.

For more information, please visit our website.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No