An Open Label Study Evaluating the Efficacy and Safety of Etrumadenant (AB928) Based Treatment Combinations in Participants With Metastatic Colorectal Cancer.
- Conditions
- Metastatic Colorectal Cancer
- Interventions
- Drug: m-FOLFOX-6 regimen
- Registration Number
- NCT04660812
- Lead Sponsor
- Arcus Biosciences, Inc.
- 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.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 227
-
Male and female participants ≥ 18 years of age
-
Histologically confirmed metastatic colorectal adenocarcinoma
-
Must have at least 1 measurable lesion per RECIST v1.1
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
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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
-
Previous anticancer treatment within 4 weeks prior to initiation of study treatment
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Prior allogeneic stem cell or solid organ transplant
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Treatment with systemic immunostimulatory agents within 4 weeks prior to initiation of study treatment
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Use of any live vaccines against infectious diseases within 28 days of first dose.
-
Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
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Current treatment with anti-viral therapy for HBV
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Structurally unstable bone lesions suggesting impending fracture
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History or leptomeningeal disease
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History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
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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
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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
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Known allergy or hypersensitivity to any of the study drugs or their excipients
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Inability to swallow medications
-
Malabsorption condition that would alter the absorption of orally administered medications
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Evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e., in the absence of therapeutic anticoagulation)
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Prior treatment with an agent targeting the adenosine pathway
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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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Etrumadenant + Zimberelimab + mFOLFOX-6 +/- Bevacizumab Etrumadenant Participants will receive oral etrumadenant in combination with zimberelimab +mFOLFOX-6 +/-bevacizumab by IV infusion. Etrumadenant + Zimberelimab + mFOLFOX-6 +/- Bevacizumab Bevacizumab Participants will receive oral etrumadenant in combination with zimberelimab +mFOLFOX-6 +/-bevacizumab by IV infusion. Etrumadenant + Zimberelimab + mFOLFOX-6 +/- Bevacizumab Zimberelimab Participants will receive oral etrumadenant in combination with zimberelimab +mFOLFOX-6 +/-bevacizumab by IV infusion. Etrumadenant + Zimberelimab + mFOLFOX-6 +/- Bevacizumab m-FOLFOX-6 regimen Participants will receive oral etrumadenant in combination with zimberelimab +mFOLFOX-6 +/-bevacizumab by IV infusion. mFOLFOX-6 +/- Bevacizumab Bevacizumab Participants will receive mFOLFOX-6 +/- bevacizumab by IV infusion. mFOLFOX-6 +/- Bevacizumab m-FOLFOX-6 regimen Participants will receive mFOLFOX-6 +/- bevacizumab by IV infusion. Regorafenib Regorafenib Participants will receive oral regorafenib AB680 + Etrumadent+ Zimberelimab AB680 Participants will receive oral etrmadenant in combination with AB680 + zimberelimab by IV infusion. AB680 + Etrumadent+ Zimberelimab Etrumadenant Participants will receive oral etrmadenant in combination with AB680 + zimberelimab by IV infusion. AB680 + Etrumadent+ Zimberelimab Zimberelimab Participants will receive oral etrmadenant in combination with AB680 + zimberelimab by IV infusion.
- Primary Outcome Measures
Name Time Method Cohort C - Objective Response Rate (ORR) From randomization until death from any cause (up to approximately 3-7 years) ORR according to RECIST v1.1, as assessed by the Investigator
Number of Participants With Treatment-emergent Adverse Events Up to approximately 10 Months Cohort A and B - Progression-free Survival (PFS) From randomization until death from any cause (up to approximately 3-7 years) PFS according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by the Investigator
- Secondary Outcome Measures
Name Time Method AUV(0-336) of Zimberelimab Cycle 1 Day 1 up to 336 hours Cohorts A and B - Objective Response Rate (ORR) From randomization until death from any cause (up to approximately 3-7 years) ORR according to RECIST v1.1 as assessed by the Investigator
Cohorts A, B, and C- Disease Control Rate (DCR) From randomization until death from any cause (up to approximately 3-7 years) DCR according to RECIST v1.1, as assessed by the Investigator
Observed Maximum Concentration (Cmax) of Etrumadenant and its Metabolites From randomization until death from any cause (up to approximately 10 months) Cycle 1 Day 1 and Cycle 2 Day 1
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) Cohorts A, B, and C- Duration of Disease Response (DoR) From randomization until death from any cause (up to approximately 3-7 years) DoR according to RECIST v1.1, as assessed by the Investigator
Cohorts A and B - Overall Survival (OS) From randomization until death from any cause (up to approximately 3-7 years) OS according to RECIST v1.1, as assessed by the Investigator
Cmax EOI of Zimberelimab Multiple timepoints up to approximately 16 months Trough Concentrations of Zimberelimab 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) Trough Concentrations of Etrumadenant and its Metabolites Multiple timepoints up to approximately 16 months 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 Number of Participants With Anti-Drug Antibodies to the Biologic Component(s) of Combination Therapy Up to approximately 10 months
Trial Locations
- Locations (51)
Clinique Sainte Anne
🇫🇷Strasbourg, France
Ircc Istituto Per La Ricerca E La Cura Del Cancro Di Candiolo Oncologia Medica
🇮🇹Candiolo, Italy
IRCCS - Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis
🇮🇹Castellana Grotte, Italy
Azienda Ospedaliero Universitaria Careggi-S.O.D. Patologia Medica
🇮🇹Firenze, Italy
Azienda Ospedaliera Niguarda Ca' Granda
🇮🇹Milano, Italy
Instituto Europeo di Oncologia
🇮🇹Milano, Italy
Istituto Clinico Humanitas IRCCS
🇮🇹Rozzano, Italy
Universita di Siena - Azienda Ospedaliera Universitaria Senese-Policlincio Santa Maria Alle Scotte
🇮🇹Siena, Italy
Chonnam National University Hwasun Hospital
🇰🇷Hwasun, Korea, Republic of
UCLA Hematology Oncology
🇺🇸Santa Monica, California, United States
University of Alabama at Birmingham Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
Arizona Clinical Research Center Inc
🇺🇸Tucson, Arizona, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Sibley Memorial Hospital
🇺🇸Washington, District of Columbia, United States
Winship Cancer Institute at Emory University
🇺🇸Atlanta, Georgia, United States
Ochsner Medical Center (OMC)
🇺🇸New Orleans, Louisiana, United States
American Oncology Partners of Maryland PA
🇺🇸Bethesda, Maryland, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Comprehensive Cancer Centers Of Nevada
🇺🇸Las Vegas, Nevada, United States
NYU Langone Medical Center - NYU Medical Oncology Associates
🇺🇸New York, New York, United States
New York-Presbyterian Hospital-Columbia University Medical Center
🇺🇸New York, New York, United States
University of Pennsylvania - Perelman Center for Advanced Medicine - Penn Radiation Oncology
🇺🇸Philadelphia, Pennsylvania, United States
Prisma Health-Upstate
🇺🇸Greenville, South Carolina, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Wisconsin School of Medicine
🇺🇸Madison, Wisconsin, United States
Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
🇫🇷Bordeaux, France
Centre Georges Francois Leclerc
🇫🇷Dijon, France
Hopital Hotel Dieu
🇫🇷Nantes Cedex 1, France
Groupe Hospitalier Pitie-Salpetriere-Centre De Recherche et de Medecine de l'Obesite
🇫🇷Paris Cedex 13, France
Hopital Saint Antoine
🇫🇷Paris, France
CHU la Miletrie
🇫🇷Poitiers, France
Seoul National University Bundang Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital (SNUH)
🇰🇷Seoul, Korea, Republic of
Severance Hospital | Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center | University of Ulsan College of Medicine
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Kyungpook National University Chilgok Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Complejo Hospitalario de Orense
🇪🇸Orense, Spain
Clinica Universidad Navarra-Sede Madrid
🇪🇸Pamplona, Spain
Corporacio Sanitaria Parc Tauli
🇪🇸Sabadell, Spain
Hospital Universitario Marques De Valdecilla
🇪🇸Santander, Spain
Belfast City Hospital
🇬🇧Belfast, Northern Ireland, United Kingdom
Aberdeen Royal Infirmary
🇬🇧Aberdeen, Scotland, United Kingdom