2021
866 RBN-2397, a novel, potent, and selective PARP7 inhibitor, induces tumor-intrinsic type I interferon responses and adaptive immunity in preclinical models and patient tumors
Kuplast-Barr K, Kuplast-Barr K, Johnson M, Patel M, Yap T, Falchook G, LoRusso P, Abo R, Liu C, Manyak E, Cleary L, Bozon V, Parasuraman S, Keilhack H, McEachern K. 866 RBN-2397, a novel, potent, and selective PARP7 inhibitor, induces tumor-intrinsic type I interferon responses and adaptive immunity in preclinical models and patient tumors. Journal For ImmunoTherapy Of Cancer 2021, 9: a907-a907. DOI: 10.1136/jitc-2021-sitc2021.866.Peer-Reviewed Original ResearchPreclinical modelsPatient tumor biopsiesTumor biopsiesAdaptive immunityCancer cellsHuman phase 1 studyTumor-specific immune memoryCD8 T cell infiltrationTumor microenvironmentPhase I clinical studyType IAdvanced solid tumorsPhase 1 studyT cell infiltrationGranzyme B expressionDurable tumor regressionAdaptive immune responsesInterferon-stimulated gene expressionImmune stimulatory effectsType I interferon responseCytosolic nucleic acidsType I interferonActivated T cellsNon-tumor tissuesI interferon response
2017
Phase 1 safety of ICOS agonist antibody JTX-2011 alone and with nivolumab (nivo) in advanced solid tumors; predicted vs observed pharmacokinetics (PK) in ICONIC.
Burris H, Callahan M, Tolcher A, Kummar S, Falchook G, Pachynski R, Tykodi S, Gibney G, Seiwert T, Gainor J, LoRusso P, Hilbert J, Apgar J, Hua F, Burke J, Lazaro M, Clancy M, Ding B, Trehu E, Yap T. Phase 1 safety of ICOS agonist antibody JTX-2011 alone and with nivolumab (nivo) in advanced solid tumors; predicted vs observed pharmacokinetics (PK) in ICONIC. Journal Of Clinical Oncology 2017, 35: 3033-3033. DOI: 10.1200/jco.2017.35.15_suppl.3033.Peer-Reviewed Original ResearchAdverse eventsTarget engagementPK dataCD4 T effector cellsGrade 3 adverse eventsGrade 1Inducible Co-StimulatorPhase 1 SafetyPrior systemic therapyAdvanced solid tumorsDose limiting toxicitiesT effector cellsPhase 1 studyHours post infusionAgonist monoclonal antibodyNon-tumor tissuesTriple-negative breastQuantitative systems pharmacology modelExposure increasesPreclinical potencyQ21 daysNeck painInfusion reactionsRegulatory cellsSystemic therapy