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

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ClinicalTrials.gov Identifier: NCT04660812
Recruitment Status : Recruiting
First Posted : December 9, 2020
Last Update Posted : November 22, 2021
Sponsor:
Information provided by (Responsible Party):
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.

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 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 247 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 AB928 Based Treatment Combinations in Patients With Metastatic Colorectal Cancer
Actual Study Start Date : May 10, 2021
Estimated Primary Completion Date : September 20, 2023
Estimated Study Completion Date : December 18, 2023

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 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
Participants 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
Participants will receive oral regorafenib
Drug: regorafenib
Regorafenib is adminstered as part of standard chemotherapy regimen

Experimental: etrumadent+ zimberelimab + AB680
Participants will receive oral etrmadenant in combination with zimberelimab +AB680 by IV infusion.
Drug: etrumadenant
Etrumadenant is a 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. Cohort A and B - Progression-free Survival (PFS) [ Time Frame: 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

  2. Cohort C - Objective Response Rate (ORR) [ Time Frame: From randomization until death from any cause (up to approximately 3-7 years) ]
    ORR according to RECIST v1.1, as assessed by the Investigator

  3. Number of Participants With Treatment-emergent Adverse Events [ Time Frame: Up to approximately 10 Months ]

Secondary Outcome Measures :
  1. Cohorts A and B - Objective Response Rate (ORR) [ Time Frame: From randomization until death from any cause (up to approximately 3-7 years) ]
    ORR according to RECIST v1.1 as assessed by the Investigator

  2. Cohorts A, B, and C- Duration of Disease Response (DoR) [ Time Frame: From randomization until death from any cause (up to approximately 3-7 years) ]
    DoR according to RECIST v1.1, as assessed by the Investigator

  3. Cohorts A, B, and C- Disease Control Rate (DCR) [ Time Frame: From randomization until death from any cause (up to approximately 3-7 years) ]
    DCR according to RECIST v1.1, as assessed by the Investigator

  4. Cohorts A and B - Overall Survival (OS) [ Time Frame: From randomization until death from any cause (up to approximately 3-7 years) ]
    OS according to RECIST v1.1, as assessed by the Investigator

  5. Observed Maximum Concentration (Cmax) of Etrumadenant and its Metabolites [ Time Frame: From randomization until death from any cause (up to approximately 10 months) ]
    Cycle 1 Day 1 and Cycle 2 Day 1

  6. Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours [AUC(0-24)] of Etrumadenant and its Metabolites [ Time Frame: Up to 24 hours following Day 1 Cycle 1 and Cycle 2 (each cycle is 28 days) ]
  7. Trough Concentrations of Etrumadenant and its Metabolites [ Time Frame: Multiple timepoints up to approximately 16 months ]
  8. Cmax End of Infusion (EOI) of AB680 [ Time Frame: At the end of infusion on Day 1 Cycle 1 and Cycle 2 (each cycle is 28 days) ]
  9. Area Under the Plasma Concentration Versus Time Curve From Time Zero to 336 Hours [AUC(0-336)] of AB680 [ Time Frame: Up to 336 hours following Day 1 Cycle and Cycle 2 (each cycle is 28 days)] ]
  10. Trough Concentrations of AB680 [ Time Frame: Multiple timepoints up to approximately 16 months ]
  11. Cmax EOI of Zimberelimab [ Time Frame: Multiple timepoints up to approximately 16 months ]
  12. AUV(0-336) of Zimberelimab [ Time Frame: Cycle 1 Day 1 up to 336 hours ]
  13. Trough Concentrations of Zimberelimab [ Time Frame: Multiple timepoints up to approximately 16 months ]
  14. Number of Participants With Anti-Drug Antibodies to the Biologic Component(s) of Combination Therapy [ Time Frame: Up to approximately 10 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 clinicaltrials@arcusbio.com

Locations
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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: November 22, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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.

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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