2021
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
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
2020
A phase I study of mRNA-2752, a lipid nanoparticle encapsulating mRNAs encoding human OX40L, IL-23, and IL-36γ, for intratumoral (iTu) injection alone and in combination with durvalumab.
Patel M, Bauer T, Jimeno A, Wang D, LoRusso P, Do K, Stemmer S, Maurice-Dror C, Geva R, Zacharek S, Laino A, Sun J, Frederick J, Zhou H, Randolph W, Cohen P, Meehan R, Sullivan R. A phase I study of mRNA-2752, a lipid nanoparticle encapsulating mRNAs encoding human OX40L, IL-23, and IL-36γ, for intratumoral (iTu) injection alone and in combination with durvalumab. Journal Of Clinical Oncology 2020, 38: 3092-3092. DOI: 10.1200/jco.2020.38.15_suppl.3092.Peer-Reviewed Original ResearchSolid tumor patientsPro-inflammatory cytokinesIL-23IL-36γTumor shrinkageTumor patientsPost-treatment tumor biopsiesSquamous cell bladder carcinomaTumor-associated immune cellsDose-escalation partAdvanced solid malignanciesGrade 3/4 toxicitiesCytokine IL-22PD-L1 expressionPD-L1 levelsPD-L1 immunohistochemistryTime of presentationAnalysis of tumorsUninjected lesionsFirst doseIL-22Elevated IFNIL-6Immunomodulatory effectsBladder carcinoma