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

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ClinicalTrials.gov Identifier: NCT04660812
Recruitment Status : Not yet recruiting
First Posted : December 9, 2020
Last Update Posted : December 9, 2020
Sponsor:
Information provided by (Responsible Party):
Arcus Biosciences, Inc.

Brief Summary:
This randomized phase 1b/2 open-label study will evaluate the efficacy of etrumadenant (AB928) treatment combinations in patients with metastatic colorectal cancer.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: etrumadenant Drug: zimberelimab Drug: mFOLFOX-6 regimen Drug: bevacizumab Drug: regorafenib Drug: AB680 Phase 1 Phase 2

Detailed Description:

This is a multicenter, open-label Phase 1b/2 study in participants with metastatic colorectal cancer that will assess the efficacy of etrumadenant.

Approximately 250 participants will be enrolled to 1 of 3 cohorts:

Cohort A) etrumadenant + zimberelimab +mFOLFOX-6 +/-bev vs mFOLFOX-6 +/-Bev

Cohort B) etrumadenant + zimberelimab +mFOLFOX-6 +/-bev 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1b/2, Open-Label, Randomized Platform Study Evaluating The Efficacy and Safety of Etrumadenant (AB928) Based Treatment Combinations in Patients With Metastatic Colorectal Cancer
Estimated Study Start Date : February 26, 2021
Estimated Primary Completion Date : September 20, 2023
Estimated Study Completion Date : December 18, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: etrumadenant + zimberelimab + mFOLFOX-6 +/- bevacizumab
Patients will receive oral etrumadenant in combination with zimberelimab +mFOLFOX-6 +/-bevacizumab by IV infusion.
Drug: etrumadenant
Dual adenosine receptor (A2aR and A2bR) antagonist
Other Name: AB928

Drug: zimberelimab
Zimberelimab is a fully human anti-PD-1 monoclononal antibody
Other Name: AB122

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

Drug: bevacizumab
Bevacizumab is administered as part of standard chemotherapy regimen

Active Comparator: mFOLFOX-6 +/-bevacizumab
Patients will receive mFOLFOX-6 +/- bevacizumab by IV infusion.
Drug: mFOLFOX-6 regimen
mFOLFOX-6 regimen is administered as part of standard chemotherapy regimen

Drug: bevacizumab
Bevacizumab is administered as part of standard chemotherapy regimen

Active Comparator: regorafenib
Patients will receive oral regorafenib
Drug: regorafenib
Regorafenib is adminstered as part of standard chemotherapy regimen

Experimental: etrumadent+ zimberelimab + AB680
Patients will receive oral etrmadenant in combination with zimberelimab +AB680 by IV infusion.
Drug: etrumadenant
Dual adenosine receptor (A2aR and A2bR) antagonist
Other Name: AB928

Drug: zimberelimab
Zimberelimab is a fully human anti-PD-1 monoclononal antibody
Other Name: AB122

Drug: AB680
AB680 is a cluster of differentiated CD73 Inhibitor




Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: Time Frame: From randomization until death from any cause (up to approximately 3-7 years) ]
    PFS as assessed by RECIST v1.1

  2. Overall Survival (OS) [ Time Frame: Time Frame: From randomization until death from any cause (up to approximately 3-7 years) ]
  3. Objective Response Rate (ORR) [ Time Frame: Time Frame: From randomization until death from any cause (up to approximately 3-7 years) ]
    ORR according to RECIST v1.1



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04660812


Contacts
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Contact: Medical Director (510)694-6200 clinicaltrialinquiry@arcusbio.com

Sponsors and Collaborators
Arcus Biosciences, Inc.
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Responsible Party: Arcus Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT04660812    
Other Study ID Numbers: ARC-9
First Posted: December 9, 2020    Key Record Dates
Last Update Posted: December 9, 2020
Last Verified: December 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Arcus Biosciences, Inc.:
mCRC
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors