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

Phase 1

Active, not recruiting

• Conditions: Metastatic Colorectal Cancer
• Interventions: Drug: Etrumadenant; Drug: Regorafenib; Drug: AB680; Drug: Zimberelimab; Drug: Bevacizumab; 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.

Study Timeline

• Study First Submitted: 2020-12-03
• Study First Submitted QC: 2020-12-03
• Study First Posted: 2020-12-09
• Study Start: 2021-05-10
• Status Verified: 2025-05
• Last Update Submitted: 2025-06-25
• Last Update Posted: 2025-06-27
• Primary Completion: 2025-07
• Study Completion: 2025-08-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 227

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 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

  • Exclusion Criteria for Cohorts A and B:

• 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

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	Zimberelimab	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	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 + Etrumadenant + Zimberelimab	AB680	Participants will receive oral etrumadenant in combination with AB680 + zimberelimab by IV infusion.
AB680 + Etrumadenant + Zimberelimab	Etrumadenant	Participants will receive oral etrumadenant in combination with AB680 + zimberelimab by IV infusion.
AB680 + Etrumadenant + Zimberelimab	Zimberelimab	Participants will receive oral etrumadenant 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
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
Number of Participants With Treatment-emergent Adverse Events	Up to approximately 10 Months

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 (44)

Corporacio Sanitaria Parc Tauli; 🇪🇸 Sabadell, Spain

Arizona Clinical Research Center Inc; 🇺🇸 Tucson, Arizona, United States

City of Hope Comprehensive Cancer Center; 🇺🇸 Duarte, California, United States

UCLA Hematology Oncology; 🇺🇸 Santa Monica, 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

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