2022
Discovery of a Series of Potent, Selective, and Orally Bioavailable Nucleoside Inhibitors of CD73 That Demonstrates In Vivo Antitumor Activity
Li J, Chen L, Billedeau R, Stanton T, Chiang J, Lee C, Li W, Steggerda S, Emberley E, Gross M, Bhupathi D, Che X, Chen J, Dang R, Huang T, Ma Y, MacKinnon A, Makkouk A, Marguier G, Neou S, Sotirovska N, Spurlock S, Zhang J, Zhang W, van Zandt M, Yuan L, Savoy J, Parlati F, Sjogren E. Discovery of a Series of Potent, Selective, and Orally Bioavailable Nucleoside Inhibitors of CD73 That Demonstrates In Vivo Antitumor Activity. Journal Of Medicinal Chemistry 2022, 66: 345-370. PMID: 36529947, DOI: 10.1021/acs.jmedchem.2c01287.Peer-Reviewed Original ResearchConceptsSuppression of CD8<sup>+</sup> T cellsCD8<sup>+</sup> T cellsAdenosine monophosphateSmall-molecule CD73 inhibitorsMouse tumor modelsEcto-5'-nucleotidaseAntitumor mechanism of actionCheckpoint inhibitorsCancer immunotherapyImmunosuppressive adenosineInhibitors of CD73Mechanism of actionT cellsCD73 activityTumor modelTumor progressionHydrolysis of adenosine monophosphateDose-dependentlyCancer patientsCD73 inhibitorsOral administrationAntitumor activityCD73CancerSerum samples
2021
ARC-9: Phase Ib/II study to evaluate etrumadenant (AB928)-based treatment combinations in patients with metastatic colorectal cancer (mCRC).
Cecchini M, Krishnan K, Giafis N, Scott J, Quah C, Bendell J. ARC-9: Phase Ib/II study to evaluate etrumadenant (AB928)-based treatment combinations in patients with metastatic colorectal cancer (mCRC). Journal Of Clinical Oncology 2021, 39: tps150-tps150. DOI: 10.1200/jco.2021.39.3_suppl.tps150.Peer-Reviewed Original ResearchMetastatic colorectal cancerStandard-of-careStandard-of-care armMFOLFOX-6Cohort BCohort AActivation of effector T cellsModified 5-fluorouracilTreated with FOLFOXDying cancer cellsDose-escalation studyEffector T cellsPhase Ib/II studyAdenosine receptor blockadeAdenosine receptor antagonistPhase 1b/2Escalation studyCurative intentReceptor blockadeOpen-labelImmunosuppressive adenosineCombination therapyPrimary endpointReceptor antagonistCohort C
2019
A phase I/Ib multicenter study to evaluate the humanized anti-CD73 antibody, CPI-006, as a single agent, in combination with CPI-444, and in combination with pembrolizumab in adult patients with advanced cancers.
Mobasher M, Miller R, Kwei L, Strahs D, Das V, Luciano G, Powderly J, Merchan J, Barve M, LoRusso P, Tripathi A, Luke J. A phase I/Ib multicenter study to evaluate the humanized anti-CD73 antibody, CPI-006, as a single agent, in combination with CPI-444, and in combination with pembrolizumab in adult patients with advanced cancers. Journal Of Clinical Oncology 2019, 37: tps2646-tps2646. DOI: 10.1200/jco.2019.37.15_suppl.tps2646.Peer-Reviewed Original ResearchSingle agentCD73 antibodyTumor growthNon-small cell lungAdequate organ functionAnti-CD73 antibodiesOpen-label trialTreatment of patientsRenal cell carcinomaSelective A2AR antagonistNumber of malignanciesKnockout mice exhibitTriple-negative breastEligible patientsMeasurable diseaseLabel trialAdult patientsStandard therapyAdvanced cancerCD73 expressionImmunosuppressive adenosineMulticenter studyUrothelial bladderCell carcinomaCell lung
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