quemliclustat (AB680) / Arcus Biosci, Gilead 
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  • ||||||||||  quemliclustat (AB680) / Arcus Biosci, Gilead
    Journal, Immunogenic cell death:  Interference of ATP-Adenosine Axis by Engineered Biohybrid for Amplifying Immunogenic Cell Death-Mediated Antitumor Immunotherapy. (Pubmed Central) -  Jul 18, 2024   
    Particularly, the designed Bc@AZTF can actively enrich in tumor sites and respond to the acidic tumor microenvironment to offload AZTF nanoparticles, which can consume intracellular ATP (iATP) content and simultaneously inhibit the ATP-adenosine axis to reduce the accumulation of adenosine, thereby alleviating adenosine-mediated immunosuppression and strikingly amplifying ICD effect. Importantly, the synergy of anti-PD-1 (?PD-1) with Bc@AZTF not only establishes a collaborative antitumor immune network to potentiate effective tumoricidal immunity but also activates long-lasting immune memory effects to manage tumor recurrence and rechallenge, presenting a new paradigm for ICD treatment combined with adenosine metabolism.
  • ||||||||||  quemliclustat (AB680) / Arcus Biosci, Gilead
    Enrollment open, Combination therapy:  ARC-8: A Study to Evaluate the Safety and Tolerability of AB680 in Participants With Gastrointestinal Malignancies (clinicaltrials.gov) -  May 23, 2024   
    P1,  N=195, Recruiting, 
    Importantly, the synergy of anti-PD-1 (?PD-1) with Bc@AZTF not only establishes a collaborative antitumor immune network to potentiate effective tumoricidal immunity but also activates long-lasting immune memory effects to manage tumor recurrence and rechallenge, presenting a new paradigm for ICD treatment combined with adenosine metabolism. Active, not recruiting --> Recruiting
  • ||||||||||  CBO421 / Cidara Therap, quemliclustat (AB680) / Arcus Biosci, Gilead
    CBO421: A novel drug Fc-conjugate to prevent tumor immune evasion via the CD73/adenosine pathway (Section 4) -  Mar 5, 2024 - Abstract #AACR2024AACR_5516;    
    CBO421 demonstrated high potency in functional cell-based assays and robust antitumor efficacy in a syngeneic mouse model. Currently, CBO421 is being advanced as a clinical development candidate for the treatment of solid cancers.
  • ||||||||||  etrumadenant (AB928) / Arcus Biosci, Gilead, quemliclustat (AB680) / Arcus Biosci, Gilead
    Phase classification, Trial completion date, Trial primary completion date, Combination therapy, Metastases:  ARC-6: Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer (clinicaltrials.gov) -  Feb 15, 2024   
    P1/2,  N=173, Active, not recruiting, 
    Recruiting --> Suspended Phase classification: P1b/2 --> P1/2 | Trial completion date: Apr 2024 --> Aug 2024 | Trial primary completion date: Apr 2024 --> Aug 2024
  • ||||||||||  Yutuo (zimberelimab) / Arcus Biosci, Gilead, quemliclustat (AB680) / Arcus Biosci, Gilead
    Trial completion date, Trial primary completion date, Metastases:  Study of Gemcitabine, Cisplatin, AB680 and AB122 During First Line Treatment of Advanced Biliary Tract Cancers (QUIC) (clinicaltrials.gov) -  Jan 3, 2024   
    P2,  N=39, Recruiting, 
    Phase classification: P1b/2 --> P1/2 | Trial completion date: Apr 2024 --> Aug 2024 | Trial primary completion date: Apr 2024 --> Aug 2024 Trial completion date: Dec 2024 --> Jul 2025 | Trial primary completion date: Jun 2024 --> Jan 2025
  • ||||||||||  quemliclustat (AB680) / Arcus Biosci, Gilead
    Enrollment closed, Trial completion date, Trial primary completion date, Combination therapy:  ARC-8: A Study to Evaluate the Safety and Tolerability of AB680 in Participants With Gastrointestinal Malignancies (clinicaltrials.gov) -  Oct 23, 2023   
    P1,  N=165, Active, not recruiting, 
    These findings systematically demonstrate the efficacy and immunoregulatory mechanism of AB680, providing a novel, efficient, and promising immunotherapeutic combination strategy for PDAC. Recruiting --> Active, not recruiting | Trial completion date: Jan 2024 --> Jun 2024 | Trial primary completion date: Jan 2024 --> Jun 2024
  • ||||||||||  etrumadenant (AB928) / Arcus Biosci, Gilead, quemliclustat (AB680) / Arcus Biosci, Gilead
    Trial completion date, Trial primary completion date, Combination therapy, Metastases:  ARC-6: Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer (clinicaltrials.gov) -  Sep 5, 2023   
    P1b/2,  N=173, Active, not recruiting, 
    Recruiting --> Active, not recruiting | Trial completion date: Jan 2024 --> Jun 2024 | Trial primary completion date: Jan 2024 --> Jun 2024 Trial completion date: Jan 2024 --> Apr 2024 | Trial primary completion date: Jan 2024 --> Apr 2024
  • ||||||||||  etrumadenant (AB928) / Arcus Biosci, Gilead, quemliclustat (AB680) / Arcus Biosci, Gilead
    Enrollment change, Trial completion date, Trial primary completion date, Combination therapy, Metastases:  ARC-6: Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer (clinicaltrials.gov) -  Aug 31, 2023   
    P1b/2,  N=173, Active, not recruiting, 
    Trial completion date: Jan 2024 --> Apr 2024 | Trial primary completion date: Jan 2024 --> Apr 2024 N=342 --> 173 | Trial completion date: May 2026 --> Jan 2024 | Trial primary completion date: May 2026 --> Jan 2024
  • ||||||||||  etrumadenant (AB928) / Arcus Biosci, Gilead, quemliclustat (AB680) / Arcus Biosci, Gilead
    Enrollment closed, Combination therapy, Metastases:  ARC-6: Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer (clinicaltrials.gov) -  Aug 16, 2023   
    P1b/2,  N=342, Active, not recruiting, 
    N=342 --> 173 | Trial completion date: May 2026 --> Jan 2024 | Trial primary completion date: May 2026 --> Jan 2024 Recruiting --> Active, not recruiting
  • ||||||||||  zimberelimab (AB122) / Arcus Biosci, Otsuka, Gilead, domvanalimab (AB154) / Arcus Biosci, Gilead, Otsuka, quemliclustat (AB680) / Arcus Biosci, Gilead
    EDGE-Lung: A Phase 2 Open-Label Platform Study to Evaluate Immunotherapy-Based Combinations in Patients with Metastatic NSCLC (Exhibit Hall) -  Jul 25, 2023 - Abstract #IASLCWCLC2023IASLC_WCLC_2259;    
    P2
    Zimberelimab (zim) is a mAb that binds PD-1 on T/NK cells, preventing PD-L1-mediated immunosuppressive effects and resulting in increased immune-mediated tumor cell death...In substudy C, patients with metastatic NSCLC who have progressed after prior platinum-based chemotherapy and anti-PD-L1 therapy will receive docetaxel (75 mg/m2 IV Q3W) in combination with either quemli (300 mg IV Q3W) or dom (1200 mg IV Q3W) in combination with zim (360 mg IV Q3W)...Other endpoints include disease control rate, progression-free survival, duration of response, overall survival, and pharmacokinetics. EDGE-Lung is currently enrolling patients in Asia-Pacific, Europe, and North America.
  • ||||||||||  etrumadenant (AB928) / Arcus Biosci, Gilead, quemliclustat (AB680) / Arcus Biosci, Gilead
    Trial completion date, Trial primary completion date, Combination therapy, Metastases:  ARC-6: Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer (clinicaltrials.gov) -  Apr 5, 2023   
    P1b/2,  N=342, Recruiting, 
    Not yet recruiting --> Recruiting Trial completion date: Dec 2025 --> May 2026 | Trial primary completion date: Apr 2023 --> May 2026
  • ||||||||||  quemliclustat (AB680) / Arcus Biosci, Gilead
    Journal:  CD73 inhibits cGAS-STING and cooperates with CD39 to promote pancreatic cancer. (Pubmed Central) -  Nov 22, 2022   
    Moreover, cGAS expression in mouse KPC tumor cells was required for anti-tumor activity of the CD73 inhibitor AB680 in vivo. Our study, thus, illuminates molecular mechanisms whereby CD73 and CD39 seemingly cooperate to promote PDAC progression.
  • ||||||||||  etrumadenant (AB928) / Arcus Biosci, Gilead, quemliclustat (AB680) / Arcus Biosci, Gilead
    Enrollment change, Trial completion date, Combination therapy, Metastases:  ARC-6: Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer (clinicaltrials.gov) -  Aug 31, 2022   
    P1b/2,  N=342, Recruiting, 
    Results showed combination therapy of RFA and a CD73 small molecule inhibitor (AB680) in vivo promoted sustained tumor growth impairment up to 10 days after treatment as evidenced by increased necrosis and anti-tumor immunity, suggesting RFA in combination with CD73 inhibitors may improve PDA patient response. N=165 --> 342 | Trial completion date: Oct 2023 --> Dec 2025
  • ||||||||||  quemliclustat (AB680) / Arcus Biosci, Gilead
    Role of the extracellular ATP/adenosine pathway in neutrophil-mediated T cell suppression in ovarian cancer microenvironment (Exhibit Hall; P946) -  Apr 8, 2022 - Abstract #IMMUNOLOGY2022IMMUNOLOGY_783;    
    CD73 inhibitor Adenosine 5'-(α,β-methylene)diphosphate also abrogated PMN suppressor function while using a different inhibitor (AB-680) had no effect...Together, these studies point to eATP as a modulator of PMN suppressor function in the TME and the potential to abrogate suppression by targeting CD39. Future studies will address the specific signaling functions of eATP on PMN in the TME that drive suppressor function.
  • ||||||||||  quemliclustat (AB680) / Arcus Biosci, Gilead
    Preclinical testing of CD73 inhibitors for pancreatic cancer immunoprevention (Section 1) -  Mar 9, 2022 - Abstract #AACR2022AACR_3611;    
    Treatment with AB680 at 10mg/kg 3x/week significantly increases tumor doubling time, significantly alters intratumoral immune cell populations, and results in a significant decrease in intratumoral adenosine levels. In addition, we observed a significant increase in infiltration of activated CD8-positive T cells indicating oral gavage delivery using AB680 reverses immunosuppression in vivo.
  • ||||||||||  quemliclustat (AB680) / Arcus Biosci, Gilead
    Journal:  Immunotherapy Strategy Targeting Programmed Cell Death Ligand 1 and CD73 with Macrophage-Derived Mimetic Nanovesicles to Treat Bladder Cancer. (Pubmed Central) -  Feb 22, 2022   
    Macrophage-derived exosome-mimetic nanovesicles (EMVs) were designed and validated as a nanoplatform for coloading and delivery of the CD73 inhibitor (AB680) and the monoclonal antibody to programmed cell death ligand 1 (aPDL1)...Moreover, the CD73 inhibitor reduced extracellular adenosine production, and the combination therapy significantly promoted the activation and infiltration of cytotoxic T-lymphocytes, which helped to optimally suppress tumor growth and extend median survival in vivo. Therefore, using EMVs to deliver a combination of aPDL1 and the CD73 inhibitor may be a useful combined immunotherapy strategy for treating bladder cancer.
  • ||||||||||  quemliclustat (AB680) / Arcus Biosci, Gilead
    Trial completion date, Trial primary completion date:  A Study to Investigate the Pharmacokinetic Profile of Oral AB680 in Healthy Volunteers (clinicaltrials.gov) -  Sep 16, 2021   
    P1,  N=32, Recruiting, 
    The data presented here support the clinical use of AB308 and provides a rationale for combination with zimberelimab and adenosine pathway blocking agents such as etrumadenant and CD73 small molecule inhibitor, AB680. Trial completion date: Aug 2021 --> Nov 2021 | Trial primary completion date: Aug 2021 --> Nov 2021
  • ||||||||||  AB680 / Arcus Biosci, Gilead
    Journal:  Discovery of Natural Product Ellagic Acid as a Potent CD73 and CD39 Dual Inhibitor. (Pubmed Central) -  Jul 24, 2021   
    Inspired by the report of the first small-molecule CD73inhibitor AB680, we describe the discovery of natural product ellagic acid as a dual CD73 and CD39 inhibitor with an IC value of 1.85 ± 0.21 μM and 0.50 ± 0.22 μM, respectively. The result of cytotoxicity assays indicated that ellagic acid is a valuable lead compound with low cytotoxicity effect for immune therapy.