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

NCT04660812

Description:

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

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: An Open Label Study Evaluating the Efficacy and Safety of AB928 Based Treatment Combinations in Patients With Metastatic Colorectal Cancer.
  • 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 IDs

  • ORG STUDY ID: ARC-9
  • NCT ID: NCT04660812

Conditions

  • Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
etrumadenantAB928etrumadenant + zimberelimab + mFOLFOX-6 +/- bevacizumab
zimberelimabAB122etrumadenant + zimberelimab + mFOLFOX-6 +/- bevacizumab
mFOLFOX-6 regimenetrumadenant + zimberelimab + mFOLFOX-6 +/- bevacizumab
bevacizumabetrumadenant + zimberelimab + mFOLFOX-6 +/- bevacizumab
regorafenibregorafenib
AB680etrumadent+ zimberelimab + AB680

Purpose

This randomized phase 1b/2 open-label study will evaluate the efficacy of etrumadenant (AB928) treatment combinations in patients 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 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.
    

Trial Arms

NameTypeDescriptionInterventions
etrumadenant + zimberelimab + mFOLFOX-6 +/- bevacizumabExperimentalPatients will receive oral etrumadenant in combination with zimberelimab +mFOLFOX-6 +/-bevacizumab by IV infusion.
  • etrumadenant
  • zimberelimab
  • mFOLFOX-6 regimen
  • bevacizumab
mFOLFOX-6 +/-bevacizumabActive ComparatorPatients will receive mFOLFOX-6 +/- bevacizumab by IV infusion.
  • mFOLFOX-6 regimen
  • bevacizumab
regorafenibActive ComparatorPatients will receive oral regorafenib
  • regorafenib
etrumadent+ zimberelimab + AB680ExperimentalPatients will receive oral etrmadenant in combination with zimberelimab +AB680 by IV infusion.
  • etrumadenant
  • zimberelimab
  • AB680

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:From randomization until death from any cause (up to approximately 3-7 years)
Safety Issue:
Description:PFS as assessed by RECIST v1.1

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Arcus Biosciences, Inc.

Trial Keywords

  • mCRC

Last Updated

May 11, 2021