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 effects516 Peripheral and tumoral immune activity in the expansion part of the first-in-human DuoBody®-PD-L1×4–1BB (GEN1046) trial
Aix S, Calvo E, Moreno V, Garralda E, Cervantes A, Ramalingam S, Pérez J, LoRusso P, Furqan M, Cho D, Muik A, Lagkadinou E, Türeci Ö, Couto S, Pencheva N, Forssmann U, Şahin U, Ahmadi T, Higgs B, Jure-Kunkel M, Melero I. 516 Peripheral and tumoral immune activity in the expansion part of the first-in-human DuoBody®-PD-L1×4–1BB (GEN1046) trial. Journal For ImmunoTherapy Of Cancer 2021, 9: a546-a546. DOI: 10.1136/jitc-2021-sitc2021.516.Peer-Reviewed Original ResearchPrior anti-PD-1 therapyAnti-PD-1 therapyPD-L1NK cellsTumor reductionAnti-PD-1 combination therapyEffector memory T cellsPD-L1 blockadePhase 1/2a trialPrior systemic therapySoluble immune mediatorsTumor PD-L1Disease control rateAdvanced solid tumorsAntitumor immune responseSubset of patientsMemory T cellsSerial blood samplesImproved clinical efficacyTumor biopsy specimensCycle 1Tumor biopsy samplesEthics committees/institutional review boardsInstitutional review boardCycle 2