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

Metastatic Colorectal Cancer Clinical Trial

— ARC-9  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04660812
• Other study ID #: ARC-9
• Secondary ID: 2020-005386-13
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: May 10, 2021
• Est. completion date: July 2024

Study information

• Verified date: May 2024
• Source: Arcus Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 227
• Est. completion date: July 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• AB680
AB680 is a cluster of differentiated CD73 Inhibitor
• Etrumadenant
Etrumadenant is a dual adenosine receptor (A2aR and A2bR) antagonist
• Zimberelimab
Zimberelimab is a fully human anti-PD-1 monoclononal antibody
• Bevacizumab
Bevacizumab is administered as part of standard chemotherapy regimen
• m-FOLFOX-6 regimen
mFOLFOX-6 regimen is administered as part of standard chemotherapy regimen
• Regorafenib
Regorafenib is adminstered as part of standard chemotherapy regimen

Locations

Country	Name	City	State
France	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	Hopital Saint Antoine	Paris
France	Groupe Hospitalier Pitie-Salpetriere-Centre De Recherche et de Medecine de l'Obesite	Paris Cedex 13
France	CHU la Miletrie	Poitiers
Italy	IRCCS - Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis	Castellana Grotte
Italy	U.O Farmeaceutica Ospealiera e Politche del Farmaco	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
Korea, Republic of	Asan Medical Center, University of Ulsan College of Medicine	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	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
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Complejo Hospitalario de Orense	Orense
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United States	Winship Cancer Institute at Emory University	Atlanta	Georgia
United States	American Oncology Partners of Maryland,PA	Bethesda	Maryland
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Prisma Health-Upstate	Greenville	South Carolina
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Comprehensive Cancer Centers Of Nevada	Las Vegas	Nevada
United States	University of Wisconsin School of Medicine	Madison	Wisconsin
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	Ochsner Medical Center (OMC)	New Orleans	Louisiana
United States	New York-Presbyterian Hospital-Columbia University Medical Center	New York	New York
United States	NYU Langone Medical Center - NYU Medical Oncology Associates	New York	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	UCLA Hematology Oncology	Santa Monica	California
United States	Arizona Clinical Research Center, Inc	Tucson	Arizona
United States	Sibley Memorial Hospital	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Arcus Biosciences, Inc.	Gilead Sciences

Countries where clinical trial is conducted

United States,  France,  Italy,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	Number of Participants With Treatment-emergent Adverse Events		Up to approximately 10 Months
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Trough Concentrations of Etrumadenant and its Metabolites		Multiple timepoints up to approximately 16 months
Secondary	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)
Secondary	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)]
Secondary	Trough Concentrations of AB680		Multiple timepoints up to approximately 16 months
Secondary	Cmax EOI of Zimberelimab		Multiple timepoints up to approximately 16 months
Secondary	AUV(0-336) of Zimberelimab		Cycle 1 Day 1 up to 336 hours
Secondary	Trough Concentrations of Zimberelimab		Multiple timepoints up to approximately 16 months
Secondary	Number of Participants With Anti-Drug Antibodies to the Biologic Component(s) of Combination Therapy		Up to approximately 10 months