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    DRUG CLASS:

    Adenosine A2A receptor antagonist

    Related drugs:
    6d
    Istradefylline Effect Protocol on Parkinson's Disease Tremor (clinicaltrials.gov)
    P4, N=27, Completed, Georgetown University | Active, not recruiting --> Completed
    Trial completion
    11d
    ARC-7: Study to Evaluate Monotherapy and Combination Immunotherapies in Participants With PD-L1 Positive Non-small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=151, Active, not recruiting, Arcus Biosciences, Inc. | Trial completion date: Feb 2025 --> Aug 2025 | Trial primary completion date: Feb 2025 --> Aug 2025
    Trial completion date • Trial primary completion date
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression • PD-L1 overexpression
    |
    Yutuo (zimberelimab) • domvanalimab (AB154) • etrumadenant (AB928)
    14d
    Immunity/metabolism dual-regulation via an acidity-triggered bioorthogonal assembly nanoplatform enhances glioblastoma immunotherapy by targeting CXCL12/CXCR4 and adenosine-A2AR pathways. (PubMed, Biomaterials)
    AMD3100 (CXCR4 antagonist) and CPI-444 (adenosine 2A receptor inhibitor) were formulated into micelles, denoted as AMD@iNPDBCO and CPI@iNPN3, respectively. Furthermore, the nanoplatform remarkably amplifies immuno-radiotherapy by potently evoking cytotoxic CD8+ T cell priming, and synergized with immune checkpoint blockade by delaying CD8+ T cell exhaustion. Our work highlights the potential of the in situ assembly nanoplatform tailored for delivery of extracellular-targeted therapeutic agents for boosting GBM immunotherapy.
    Journal
    |
    CD8 (cluster of differentiation 8) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • CXCL12 (C-X-C Motif Chemokine Ligand 12)
    |
    ciforadenant (CPI-444) • plerixafor
    1m
    A2A receptor antagonist 4-(2-((6-Amino-9-ethyl-8-(furan-2-yl)-9H-purin-2-yl)amino)ethyl)phenol, a promising adenosine derivative for glioblastoma treatment. (PubMed, Eur J Pharm Sci)
    The A2AAR-ANR 672 interaction profile showed well-defined hydrogen bonds and hydrophobic contacts, indicating a typical binding mechanism inside the receptor pocket and a higher degree of conformational flexibility than the A2AAR-Istradefylline complex...Our findings shed light on how ANR 672 exerts its GBM-suppressive effect through the interaction of A2AAR. These preclinical results suggest that A2AAR blockade could be a unique strategy for treating GBM.
    Journal
    |
    ADORA2A (Adenosine A2a Receptor)
    2ms
    A Study of JNJ-86974680 in Participants With Advanced Non-small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=126, Recruiting, Johnson & Johnson Enterprise Innovation Inc. | N=76 --> 126 | Trial completion date: Aug 2028 --> Jun 2029
    Enrollment change • Trial completion date
    |
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR mutation
    |
    cetrelimab (JNJ-63723283)
    3ms
    The purpose of this study is to assess the safety, tolerability, and pharmacokinetics of increasing oral doses of INCB106385 in healthy adult participants, and the effect of food on pharmacokinetics, as well as drug interaction with a Proton Pump Inhibitor (PPI) esomeprazole. (ACTRN12620000630910)
    P1, N=84, Completed, Incyte Corporation | Not yet recruiting --> Completed
    Trial completion
    |
    INCB106385
    3ms
    ARC-4: A Study to Evaluate Immunotherapy Combinations in Participants With Lung Cancer (clinicaltrials.gov)
    P1, N=77, Completed, Arcus Biosciences, Inc. | Active, not recruiting --> Completed
    Trial completion
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation
    |
    Keytruda (pembrolizumab) • carboplatin • pemetrexed • Yutuo (zimberelimab) • etrumadenant (AB928)
    3ms
    Istradefylline for Parkinson Disease With Cognitive Impairment (clinicaltrials.gov)
    P2, N=10, Active, not recruiting, Virginia Commonwealth University | Recruiting --> Active, not recruiting
    Enrollment closed
    3ms
    Evolution of myeloid-mediated immunotherapy resistance in prostate cancer. (PubMed, Nature)
    Consistent with preclinical results, inhibition of A2ARs using ciforadenant in combination with programmed death 1 ligand 1 (PD-L1) blockade using atezolizumab induces clinical responses in patients with mCRPC. Moreover, inhibiting A2ARs results in a significant decrease in SPP1hi-TAM abundance in CRPC, indicating that this pathway is involved in both induction and downstream immunosuppression. Collectively, these findings establish SPP1hi-TAMs as key mediators of ICI resistance in mCRPC through adenosine signalling, emphasizing their importance as both a therapeutic target and a potential biomarker for predicting treatment efficacy.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • SPP1 (Secreted Phosphoprotein 1) • ADORA2A (Adenosine A2a Receptor)
    |
    Tecentriq (atezolizumab) • ciforadenant (CPI-444)
    4ms
    ARC-9: An Open Label Study Evaluating the Efficacy and Safety of Etrumadenant (AB928) Based Treatment Combinations in Participants With Metastatic Colorectal Cancer. (clinicaltrials.gov)
    P1/2, N=227, Active, not recruiting, Arcus Biosciences, Inc. | Trial completion date: Oct 2024 --> Jul 2025 | Trial primary completion date: Oct 2024 --> Jul 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    Avastin (bevacizumab) • 5-fluorouracil • Stivarga (regorafenib) • Yutuo (zimberelimab) • leucovorin calcium • etrumadenant (AB928) • quemliclustat (AB680)
    4ms
    Adenosine 2A Receptor Antagonism and AIH in ALS (clinicaltrials.gov)
    P1/2, N=40, Recruiting, University of Florida | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Oct 2024 --> Dec 2025
    Trial completion date • Trial primary completion date
    4ms
    A Study of ILB2109 in Patients With Advanced Solid Malignancies (clinicaltrials.gov)
    P1, N=48, Active, not recruiting, Innolake Biopharm | Recruiting --> Active, not recruiting | Trial primary completion date: Aug 2024 --> Dec 2024
    Enrollment closed • Trial primary completion date • Metastases
    |
    ILB-2109
    5ms
    The A2AR antagonist inupadenant promotes humoral responses in patients (ESMO-IO 2024)
    These effects may play a substantial role in delaying progression in end-stage patients. Additional work is ongoing to demonstrate this new mechanism of action across clinical settings and patient populations.
    Clinical
    |
    CXCL13 (Chemokine (C-X-C motif) ligand 13) • ADORA2A (Adenosine A2a Receptor)
    |
    CXCL13 expression
    |
    nCounter® PanCancer IO 360™ Panel
    |
    inupadenant (EOS-850)
    6ms
    PANTHER: A Phase I-II Study to Test the Safety and Efficacy of PD1 (AB122) and Adenosine Receptor (AB928) Antagonists With Chemotherapy After Short-Course Radiation for Rectal Cancer. (clinicaltrials.gov)
    P2, N=43, Recruiting, Weill Medical College of Cornell University | Trial completion date: Dec 2027 --> Dec 2030
    Trial completion date
    |
    5-fluorouracil • Yutuo (zimberelimab) • leucovorin calcium • etrumadenant (AB928)
    6ms
    New Formulation Study of Inupadenant (EOS100850) in Patients with Cancer (clinicaltrials.gov)
    P1, N=57, Completed, iTeos Therapeutics | Recruiting --> Completed | Trial completion date: Nov 2023 --> May 2024 | Trial primary completion date: Oct 2023 --> May 2024
    Trial completion • Trial completion date • Trial primary completion date • Metastases
    |
    inupadenant (EOS-850)
    6ms
    Keynote A54: First-in-Human Study of EOS100850 (Inupadenant) in Patients with Cancer (clinicaltrials.gov)
    P1, N=119, Completed, iTeos Therapeutics | Active, not recruiting --> Completed | Trial primary completion date: Jun 2023 --> May 2024
    Trial completion • Trial primary completion date • Combination therapy • Metastases
    |
    Keytruda (pembrolizumab) • carboplatin • paclitaxel • inupadenant (EOS-850)
    6ms
    ARC-6: Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer (clinicaltrials.gov)
    P1/2, N=173, Completed, Arcus Biosciences, Inc. | Active, not recruiting --> Completed
    Trial completion • Combination therapy • Metastases
    |
    docetaxel • Xtandi (enzalutamide) • Yutuo (zimberelimab) • Trodelvy (sacituzumab govitecan-hziy) • etrumadenant (AB928) • quemliclustat (AB680)
    7ms
    Dual A2A/ A2B adenosine receptor antagonist M1069 counteracts immuno-suppressive mechanisms of adenosine and reduces tumor growth in vivo. (PubMed, Mol Cancer Ther)
    In vivo, M1069 decreased tumor growth as a monotherapy and enhanced anti-tumor activity of bintrafusp alfa (BA) or cisplatin in syngeneic adenosinehi/CD73hi 4T1 breast tumor model, but not in the CD73 knockout (KO) 4T1 tumor model or in adenosinelow/CD73low MC38 murine colon carcinoma model. In summary, our dual A2A/A2B AR antagonist M1069 may counteract immune-suppressive mechanisms of high concentrations of adenosine in vitro and in vivo and enhance the anti-tumor activity of other agents, including BA and cisplatin.
    Preclinical • Journal
    |
    CD73 (5'-Nucleotidase Ecto) • IL2 (Interleukin 2) • CXCL5 (Chemokine (C-X-C motif) ligand 5) • CXCL1 (Chemokine (C-X-C motif) ligand 1)
    |
    cisplatin • bintrafusp alfa (M7824) • M1069
    8ms
    ARC-4: A Study to Evaluate Immunotherapy Combinations in Participants With Lung Cancer (clinicaltrials.gov)
    P1, N=77, Active, not recruiting, Arcus Biosciences, Inc. | Trial completion date: Aug 2024 --> Nov 2024 | Trial primary completion date: Aug 2024 --> Nov 2024
    Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor)
    |
    Keytruda (pembrolizumab) • carboplatin • pemetrexed • Yutuo (zimberelimab) • etrumadenant (AB928)
    8ms
    ARC-9: An Open Label Study Evaluating the Efficacy and Safety of Etrumadenant (AB928) Based Treatment Combinations in Participants With Metastatic Colorectal Cancer. (clinicaltrials.gov)
    P1/2, N=227, Active, not recruiting, Arcus Biosciences, Inc. | Trial completion date: Jul 2024 --> Oct 2024 | Trial primary completion date: Jul 2024 --> Oct 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    Avastin (bevacizumab) • 5-fluorouracil • Stivarga (regorafenib) • Yutuo (zimberelimab) • leucovorin calcium • etrumadenant (AB928) • quemliclustat (AB680)
    9ms
    Nociceptive adenosine A2A receptor on trigeminal nerves orchestrates CGRP release to regulate the progression of oral squamous cell carcinoma. (PubMed, Int J Oral Sci)
    We further demonstrated the pro-tumor effect of CGRP by feeding mice with the clinically approved CGRP receptor antagonist rimegepant which inhibited the activation of ERK and YAP. Finally, we diminished the impact of CGRP on OSCC with istradefylline, a clinically available drug that targets neuronal A2AR. Therefore, we established trigeminal A2AR-mediated CGRP release as a promising druggable circuit in OSCC treatment.
    Journal
    |
    CD73 (5'-Nucleotidase Ecto) • ADORA2A (Adenosine A2a Receptor)
    10ms
    Discovery of a potent, selective, and tumor-suppressing antibody antagonist of adenosine A2A receptor. (PubMed, PLoS One)
    Lead candidate TB206-001 displayed nanomolar binding of hA2AR-overexpressing HEK293 cells; cross-reactivity with mouse and cynomolgus A2AR but not human A1, A2B, or A3 receptors; functional antagonism of hA2AR in hA2AR-overexpressing HEK293 cells and peripheral blood mononuclear cells (PBMCs); and tumor-suppressing activity in colon tumor-bearing HuCD34-NCG mice. Given its therapeutic properties, TB206-001 is a good candidate for incorporation into next-generation bispecific immunotherapeutics.
    Journal
    |
    ADORA2A (Adenosine A2a Receptor)
    10ms
    A Study of ILB2109 and Toripalimab in Patients With Advanced Solid Malignancies (clinicaltrials.gov)
    P1/2, N=200, Recruiting, Innolake Biopharm | Not yet recruiting --> Recruiting
    Enrollment open
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • CD68 (CD68 Molecule)
    |
    PD-L1 expression
    |
    Loqtorzi (toripalimab-tpzi) • ILB-2109
    10ms
    A Study of ILB2109 in Patients With Advanced Solid Malignancies (clinicaltrials.gov)
    P1, N=48, Recruiting, Innolake Biopharm | Trial completion date: Jan 2024 --> Feb 2025 | Trial primary completion date: Nov 2023 --> Aug 2024
    Trial completion date • Trial primary completion date
    |
    ILB-2109
    11ms
    SBRT-AMICO: Adenosine Signaling Modulation and Immune Checkpoint Inhibition With Hormone Sensitive Oligometastatic Prostate Cancer (clinicaltrials.gov)
    P2, N=23, Recruiting, Catherine Spina | Trial primary completion date: Apr 2024 --> Dec 2025
    Trial primary completion date • Checkpoint inhibition • Metastases
    |
    Yutuo (zimberelimab) • etrumadenant (AB928) • quemliclustat (AB680)
    11ms
    ADPORT-601: TT-10 as a Single Agent in Subjects With Advanced Selected Solid Tumors (clinicaltrials.gov)
    P1/2, N=90, Active, not recruiting, Portage Biotech | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    PORT-6
    11ms
    Safety and Efficacy of Zimberelimab (AB122) in Combination With Domvanalimab (AB154) and Etrumadenant (AB928) in Patients With Previously Treated Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P2; Recruiting --> Active, not recruiting
    Combination therapy • Enrollment closed
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    PD-L1 IHC 22C3 pharmDx
    |
    Yutuo (zimberelimab) • domvanalimab (AB154) • etrumadenant (AB928)
    1year
    INCB106385 Alone or in Combination With Immunotherapy in Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=54, Completed, Incyte Corporation | Active, not recruiting --> Completed
    Trial completion • Combination therapy • Metastases
    |
    CD8 (cluster of differentiation 8)
    |
    Zynyz (retifanlimab-dlwr) • INCB106385
    1year
    Phase 1b/2 Trial of Ipilimumab, Nivolumab, and Ciforadenant (Adenosine A2a Receptor Antagonist) in First-line Advanced Renal Cell Carcinoma. (clinicaltrials.gov)
    P1/2, N=24, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • ciforadenant (CPI-444)
    1year
    Phase 1b/2 Trial of Ipilimumab, Nivolumab, and Ciforadenant (Adenosine A2a Receptor Antagonist) in First-line Advanced Renal Cell Carcinoma. (clinicaltrials.gov)
    P1/2, N=24, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting
    Enrollment open
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • ciforadenant (CPI-444)
    1year
    Effect of Istradefylline Treatment on Behavioral Measures of Apathy in Parkinson's Disease. (clinicaltrials.gov)
    P=N/A, N=8, Terminated, Medical University of South Carolina | Active, not recruiting --> Terminated; recruitment issues
    Trial termination
    1year
    ARC-6: Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer (clinicaltrials.gov)
    P1/2, N=173, Active, not recruiting, Arcus Biosciences, Inc. | Phase classification: P1b/2 --> P1/2 | Trial completion date: Apr 2024 --> Aug 2024 | Trial primary completion date: Apr 2024 --> Aug 2024
    Phase classification • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    docetaxel • Xtandi (enzalutamide) • Yutuo (zimberelimab) • Trodelvy (sacituzumab govitecan-hziy) • etrumadenant (AB928) • quemliclustat (AB680)
    1year
    An Open Label Study Evaluating the Efficacy and Safety of Etrumadenant (AB928) Based Treatment Combinations in Participants With Metastatic Colorectal Cancer. (clinicaltrials.gov)
    P1/2, N=227, Active, not recruiting, Arcus Biosciences, Inc. | Phase classification: P1b/2 --> P1/2 | Trial completion date: Jan 2024 --> Jul 2024 | Trial primary completion date: Jan 2024 --> Jul 2024
    Phase classification • Trial completion date • Trial primary completion date • Metastases
    |
    Avastin (bevacizumab) • 5-fluorouracil • Stivarga (regorafenib) • Yutuo (zimberelimab) • leucovorin calcium • etrumadenant (AB928) • quemliclustat (AB680)
    1year
    Phase 1b/2 Trial of Ipilimumab, Nivolumab, and Ciforadenant (Adenosine A2a Receptor Antagonist) in First-line Advanced Renal Cell Carcinoma. (clinicaltrials.gov)
    P1/2, N=24, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1/2 | N=15 --> 24
    Enrollment closed • Phase classification • Enrollment change • Metastases
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • ciforadenant (CPI-444)
    1year
    A Phase 1 Study of YZJ-5053 Tablets in Participants With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=157, Recruiting, Shanghai Haiyan Pharmaceutical Technology Co., Ltd.
    New P1 trial • Metastases
    1year
    CPI-006 Alone and in Combination With Ciforadenant and With Pembrolizumab for Patients With Advanced Cancers (clinicaltrials.gov)
    P1, N=117, Completed, Corvus Pharmaceuticals, Inc. | Active, not recruiting --> Completed | N=378 --> 117 | Trial completion date: Dec 2025 --> Feb 2023 | Trial primary completion date: Dec 2023 --> Dec 2022
    Trial completion • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    MSI (Microsatellite instability)
    |
    Keytruda (pembrolizumab) • ciforadenant (CPI-444) • mupadolimab (CPI-006)
    over1year
    Safety and pharmacokinetics of imaradenant (AZD4635) in Japanese patients with advanced solid malignancies: a phase I, open-label study. (PubMed, Cancer Chemother Pharmacol)
    No new or unexpected safety concerns were identified, and imaradenant had an acceptable safety profile at both 50- and 75-mg QD.
    PK/PD data • Journal • Metastases
    |
    ADORA2A (Adenosine A2a Receptor)
    |
    imaradenant (AZD4635)
    over1year
    Istradefylline Effect Protocol on Parkinson's Disease Tremor (clinicaltrials.gov)
    P4, N=27, Active, not recruiting, Georgetown University | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Sep 2023 --> Sep 2024
    Enrollment closed • Trial completion date • Trial primary completion date
    over1year
    Study to Assess EXS21546 in Combination in Patients With Advanced Solid Tumours (clinicaltrials.gov)
    P1b/2a, N=6, Terminated, Exscientia AI Limited | N=110 --> 6 | Trial completion date: Mar 2026 --> Oct 2023 | Recruiting --> Terminated | Trial primary completion date: Sep 2025 --> Sep 2023; Emerging data demonstrates challenge for EXS21546 to reach suitable therapeutic index.
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy • Metastases
    |
    EXS21546
    over1year
    ARC-7: Study to Evaluate Monotherapy and Combination Immunotherapies in Participants With PD-L1 Positive Non-small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=151, Active, not recruiting, Arcus Biosciences, Inc. | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Feb 2025
    Trial completion date • Trial primary completion date • Combination therapy
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression • PD-L1 overexpression
    |
    Yutuo (zimberelimab) • domvanalimab (AB154) • etrumadenant (AB928)
    over1year
    PANTHEoN: A Study of Concurrent Chemoradiation in Combination With or Without PD1 Inhibitor AB122 Adenosine 2a Receptor / Adenosine 2b Receptor Inhibitor AB928 Therapies in Locally Advanced Head and Neck Cancers (clinicaltrials.gov)
    P1, N=0, Withdrawn, Jennifer Choe | N=24 --> 0 | Not yet recruiting --> Withdrawn
    Enrollment change • Trial withdrawal • Combination therapy • IO biomarker • Metastases
    |
    cisplatin • Yutuo (zimberelimab) • etrumadenant (AB928)
    over1year
    An Open Label Study Evaluating the Efficacy and Safety of Etrumadenant (AB928) Based Treatment Combinations in Participants With Metastatic Colorectal Cancer. (clinicaltrials.gov)
    P1b/2, N=227, Active, not recruiting, Arcus Biosciences, Inc. | Trial primary completion date: Sep 2023 --> Jan 2024
    Trial primary completion date • Metastases
    |
    Avastin (bevacizumab) • 5-fluorouracil • Stivarga (regorafenib) • Yutuo (zimberelimab) • leucovorin calcium • etrumadenant (AB928) • quemliclustat (AB680)