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 response539 Phase 1 study of mRNA-2752, a lipid nanoparticle encapsulating mRNAs encoding human OX40L/IL-23/IL-36γ, for intratumoral (ITu) injection +/- durvalumab in advanced solid tumors and lymphoma
Patel M, Jimeno A, Wang D, Stemmer S, Bauer T, Sweis R, Geva R, Kummar S, Reagan P, Perets R, LoRusso P, Gupta S, Zacharek S, Laino A, Milberg O, Frederick J, Chen S, Pascarella S, Randolph W, Aanur P, Johansen L, Do K, Meehan R, Sullivan R. 539 Phase 1 study of mRNA-2752, a lipid nanoparticle encapsulating mRNAs encoding human OX40L/IL-23/IL-36γ, for intratumoral (ITu) injection +/- durvalumab in advanced solid tumors and lymphoma. 2021, a569-a569. DOI: 10.1136/jitc-2021-sitc2021.539.Peer-Reviewed Original ResearchIL-23 serum concentrationsTreatment-emergent adverse eventsPro-inflammatory cytokinesIL-23IL-36γArm BSerum concentrationsAST/ALT increasePD-L1 inhibitor durvalumabPost-treatment tumor biopsiesSquamous cell bladder cancerPK/PD modelingEmergent adverse eventsPain/swellingPD-L1 blockadeCytokine release syndromeAdvanced solid tumorsCytokine IL-22PD-L1 levelsPhase 1 studyPK/PD modelT cell infiltrationEthics BoardGood clinical practiceTreatment effects