First-in-Human Phase I Trial of a Tumor-Targeted Cytokine (NHS-IL12) in Subjects with Metastatic Solid Tumors
Strauss J, Heery CR, Kim JW, Jochems C, Donahue RN, Montgomery AS, McMahon S, Lamping E, Marté J, Madan RA, Bilusic M, Silver MR, Bertotti E, Schlom J, Gulley JL. First-in-Human Phase I Trial of a Tumor-Targeted Cytokine (NHS-IL12) in Subjects with Metastatic Solid Tumors. Clinical Cancer Research 2019, 25: 99-109. PMID: 30131389, PMCID: PMC6320276, DOI: 10.1158/1078-0432.ccr-18-1512.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCell Line, TumorDNA FragmentationDrug-Related Side Effects and Adverse ReactionsFemaleHumansImmunoglobulin GInfluenza, HumanInterleukin-12Killer Cells, NaturalLymphocytes, Tumor-InfiltratingMaleMaximum Tolerated DoseMiddle AgedNatural Killer T-CellsNeoplasmsNeoplasms, Second PrimaryReceptors, Antigen, T-CellRecombinant Fusion ProteinsTransaminasesConceptsTreatment-related adverse eventsAscending dose cohortsNHS-IL12Solid tumorsT-cell receptor sequencing analysisHuman phase I trialMultiple ascending dose cohortsSingle ascending dose (SAD) cohortsTumor-infiltrating lymphocyte densityPeripheral blood mononuclear cellsPeripheral immune cell subsetsDurable stable diseaseImmune checkpoint inhibitorsObjective tumor responsePhase II doseT-cell receptor diversityAdvanced solid tumorsFlu-like symptomsMetastatic solid tumorsPhase I trialNatural killer cellsImmune cell subsetsBlood mononuclear cellsWarrants further studyEnhanced antitumor activity