生物活性

• 描述Adenosine signaling through the A2A adenosine receptor(A2AR) on immune cells is a critical regulator of inflammation and immune response which has been shown to suppress antitumor immunity and limit the efficacy of immunotherapy, chemotherapy, adoptive cell transfer therapies, and vaccines in preclinical models. CPI-444 is an orally administered antagonist of the A2AR with a K_i of 3.54 nM. C57BL/6 mice immunized with vaccinia-OVA showed a signifcant enhancement in the antigen-specifc CD8+ T cell response when treated with CPI-444 (10 mg/kg, p.o. daily for 5 days starting 1 day post-infection) compared with models^[2]. Anti-PD-1 and CPI-444(100 mg/kg, 12 days) combination treatment showed a significant improvement in tumor regression and animal survival in both CT26 and MC38 tumor models, compared with anti-PD-1 treatment alone. Phase 1b clinical trial in patients with non-small cell lung, melanoma, renal, triple negative breast, and other (head and neck, colorectal [MSI-H], bladder) tumors demonstrated that NECA(adenosine analog) signaling was robustly inhibited at the doses selected in CPI-444 treatment^[3].

• 动物研究
  剂量	Mice: 1 mg/kg - 100 mg/kg[1] (p.o.)
  给药途径	p.o.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT03708224	Cancer Carcin... more >>oma Squamous Cell Carcinoma Head and Neck Cancer Collapse <<	Phase 2	Not yet recruiting	November 30, 2025	United States, California ... more >> University of San Francisco, California San Francisco, California, United States, 94115 Collapse <<
  NCT03337698	Carcinoma, Non-Small-Cell Lung	Phase 1 Phase 2	Recruiting	April 20, 2022	United States, Connecticut ... more >> Smilow Cancer Hospital at Yale New Haven Recruiting New Haven, Connecticut, United States, 06510 United States, Massachusetts Massachusetts General Hospital Not yet recruiting Boston, Massachusetts, United States, 02114 Dana-Farber Cancer Institute Recruiting Boston, Massachusetts, United States, 02215 United States, New York Columbia University Medical Center; Research Pharmacy, Irving Pavillion, Ip 7-749 Recruiting New York, New York, United States, 10032 United States, Tennessee Sarah Cannon Research Institute Recruiting Nashville, Tennessee, United States, 37203 Australia, Victoria Peter Mac Callum Cancer Center Recruiting East Melbourne, Victoria, Australia, 3002 France Centre Léon Bérard Recruiting Lyon, France, 69008 Hôpital Nord Not yet recruiting Marseille, France, 13915 Institut Universitaire du Cancer de Toulouse-Oncopole; PHARMACIE Recruiting Toulouse, France, 31100 Korea, Republic of Seoul National University Hospital Recruiting Seoul, Korea, Republic of, 03080 Severance Hospital, Yonsei University Health System; Pharmacy Recruiting Seoul, Korea, Republic of, 03722 University of Ulsan College of Medicine - Asan Medical Center (AMC) - Asan Cancer Center (ACC) Recruiting Songpa-gu, Korea, Republic of, 05505 Spain Clínica Universidad de Navarra Recruiting Pamplona, Navarra, Spain, 31620 Hospital Universitari Vall d'Hebron Recruiting Barcelona, Spain, 08035 Fundación Jimenez Díaz Recruiting Madrid, Spain, 28040 South Texas Accelerated Research Therapeutics Madrid - CIOCC - Universitario Sanchinarro Recruiting Madrid, Spain, 28050 United Kingdom Barts Cancer Institute Recruiting London, United Kingdom, E1 2AT Royal Marsden Hospital; Institute of Cancer Research Recruiting Sutton, United Kingdom, SM2 5PT Collapse <<
  NCT03454451	Non-Small Cell Lung Cancer ... more >> Renal Cell Cancer Colorectal Cancer Triple Negative Breast Cancer Cervical Cancer Ovarian Cancer Pancreatic Cancer Endometrial Cancer Sarcoma Squamous Cell Carcinoma of the Head and Neck Bladder Cancer Metastatic Castration Resistant Prostate Cancer Collapse <<	Phase 1	Recruiting	December 2023	United States, Connecticut ... more >> Yale School of Medicine Recruiting New Haven, Connecticut, United States, 06519 Contact: Site Coordinator    203-785-3482    ycci@yale.edu    Principal Investigator: Patricia LoRusso, MD          United States, Florida University of Miami Recruiting Miami, Florida, United States, 33136 Contact: Study Coordinator    305-243-0865    txl351@med.miami.edu    Principal Investigator: Jaime Merchan, MD          United States, Illinois The University of Chicago Recruiting Chicago, Illinois, United States, 60637 Contact: Site Coordinator    773-702-1835    mweist@medicine.bsd.uchicago.edu    Principal Investigator: Jason Luke, MD          United States, New York Icahn School of Medicine at Mount Sinai Recruiting New York, New York, United States, 10029 Contact: Site Coordinator    212-824-7309    ccto@mssm.edu    Principal Investigator: Thomas Marron, MD          United States, North Carolina Carolina BioOncology Institute Recruiting Huntsville, North Carolina, United States, 28078 Contact: Study Coordinator    704-947-6599    info@carolinabiooncology.org    Principal Investigator: John Powderly          United States, Oklahoma University of Oklahoma - Stephenson Cancer Center Recruiting Oklahoma City, Oklahoma, United States, 73104 Contact: Site Coordinator    405-271-1112    SCC-Clinical-Trials-Office@ouhsc.edu    Principal Investigator: Abhishek Tripathi, MD          United States, Tennessee Sarah Cannon Research Institute Recruiting Nashville, Tennessee, United States, 37203 Contact: Site Coordinator    615-329-7274    asksarah@sarahcannon.com    Principal Investigator: Melissa Johnson, MD          United States, Texas Mary Crowley Cancer Research Recruiting Dallas, Texas, United States, 75230 Contact: Study Coordinator    972-566-3000    information@marycrowley.org    Principal Investigator: Minal Barve, MD          United States, Wisconsin Froedtert Hospital & Medical College of Wisconsin Recruiting Milwaukee, Wisconsin, United States, 53226 Contact: Site Coordinator    414-805-8900    CCCTO@mcw.edu    Principal Investigator: Matthew Riese, MD Collapse <<

• 更多
• 参考文献

• [1] Willingham SB, Ho PY, et al. A2AR Antagonism with CPI-444 Induces Antitumor Responses and Augments Efficacy to Anti-PD-(L)1 and Anti-CTLA-4 in Preclinical Models. Cancer Immunol Res. 2018 Oct;6(10):1136-1149.

  [2] Leone RD, Sun IM, Oh MH, Sun IH, Wen J, Englert J, Powell JD. Inhibition of the adenosine A2a receptor modulates expression of T cell coinhibitory receptors and improves effector function for enhanced checkpoint blockade and ACT in murine cancer models. Cancer Immunol Immunother. 2018 Aug;67(8):1271-1284. doi: 10.1007/s00262-018-2186-0. Epub 2018 Jun 19. PMID: 29923026.

  [3] Abstract PR04: CPI-444: A potent and selective inhibitor of A2AR induces antitumor responses alone and in combination with anti-PD-L1 in preclinical and clinical studies