2019
A First-in-Human Study and Biomarker Analysis of NKTR-214, a Novel IL2Rβγ-Biased Cytokine, in Patients with Advanced or Metastatic Solid Tumors
Bentebibel SE, Hurwitz ME, Bernatchez C, Haymaker C, Hudgens CW, Kluger HM, Tetzlaff MT, Tagliaferri MA, Zalevsky J, Hoch U, Fanton C, Aung S, Hwu P, Curti BD, Tannir NM, Sznol M, Diab A. A First-in-Human Study and Biomarker Analysis of NKTR-214, a Novel IL2Rβγ-Biased Cytokine, in Patients with Advanced or Metastatic Solid Tumors. Cancer Discovery 2019, 9: 711-721. PMID: 30988166, DOI: 10.1158/2159-8290.cd-18-1495.Peer-Reviewed Original ResearchConceptsNKTR-214Tumor biopsiesDurable disease stabilizationImmuno-oncology agentsMulticenter phase IPathway-targeted agentsTreatment tumor biopsiesPhase II doseActivation of CD8Metastatic solid tumorsNatural killer cellsOutpatient regimenCheckpoint inhibitorsDisease stabilizationRegulatory cellsEffector phenotypeKiller cellsTreatment algorithmImmune activationTumor shrinkagePharmacodynamic markersImmune cellsClinical activityIL2 receptorHuman studies
2018
NKTR-214 (CD122-biased agonist) plus nivolumab in patients with advanced solid tumors: Preliminary phase 1/2 results of PIVOT.
Diab A, Hurwitz M, Cho D, Papadimitrakopoulou V, Curti B, Tykodi S, Puzanov I, Ibrahim N, Tolaney S, Tripathy D, Gao J, Siefker-Radtke A, Clemens W, Tagliaferri M, Gettinger S, Kluger H, Larkin J, Grignani G, Sznol M, Tannir N. NKTR-214 (CD122-biased agonist) plus nivolumab in patients with advanced solid tumors: Preliminary phase 1/2 results of PIVOT. Journal Of Clinical Oncology 2018, 36: 3006-3006. DOI: 10.1200/jco.2018.36.15_suppl.3006.Peer-Reviewed Original Research
2017
Effect of a novel IL-2 cytokine immune agonist (NKTR-214) on proliferating CD8+T cells and PD-1 expression on immune cells in the tumor microenvironment in patients with prior checkpoint therapy.
Bernatchez C, Haymaker C, Hurwitz M, Kluger H, Tetzlaff M, Jackson N, Gergel I, Tagliaferri M, Zalevsky J, Hoch U, Fanton C, Iacucci E, Aung S, Imperiale M, Liao E, Bentebibel S, Tannir N, Hwu P, Sznol M, Diab A. Effect of a novel IL-2 cytokine immune agonist (NKTR-214) on proliferating CD8+T cells and PD-1 expression on immune cells in the tumor microenvironment in patients with prior checkpoint therapy. Journal Of Clinical Oncology 2017, 35: 2545-2545. DOI: 10.1200/jco.2017.35.15_suppl.2545.Peer-Reviewed Original ResearchNKTR-214PD-1 expressionT-cell clonalityTumor microenvironmentNK cellsCell clonalityIL-2 receptor pathwayDays post doseDrug-related AEsImmune-related AEAnti-PD1 therapyCapillary leak syndromePhase 1/2 trialMetastatic solid tumorsFavorable safety profileImmune checkpoint genesSignificant tumor regressionTumor tissue samplesGene expression analysisCytotoxic markersEffector CD8Leak syndromeCheckpoint therapyPrior immunotherapyRegulatory cellsA phase 1/2 study of a novel IL-2 cytokine, NKTR-214, and nivolumab in patients with select locally advanced or metastatic solid tumors.
Diab A, Tannir N, Bernatchez C, Haymaker C, Bentebibel S, Curti B, Wong M, Gergel I, Tagliaferri M, Zalevsky J, Hoch U, Aung S, Imperiale M, Cho D, Tykodi S, Puzanov I, Kluger H, Hurwitz M, Hwu P, Sznol M. A phase 1/2 study of a novel IL-2 cytokine, NKTR-214, and nivolumab in patients with select locally advanced or metastatic solid tumors. Journal Of Clinical Oncology 2017, 35: e14040-e14040. DOI: 10.1200/jco.2017.35.15_suppl.e14040.Peer-Reviewed Original ResearchNKTR-214Phase 1/2 studyT cellsIL-2 receptor pathwayTumor immune cell infiltratesTumor microenvironmentNivolumab combination therapyDose limiting toxicitiesImmune cell infiltratesUnconfirmed complete responseMetastatic solid tumorsWeeks of treatmentFavorable safety profileIL-2 pathwayIL-2 cytokineT-cell clonalityBiomarker dataTumor response dataImmunotherapy-naïveMonotherapy trialsQ3w scheduleRECIST 1.1Checkpoint inhibitorsEffector CD8Adverse eventsEffect of NKTR-214 on the number and activity of CD8+ tumor infiltrating lymphocytes in patients with advanced renal cell carcinoma.
Hurwitz M, Diab A, Bernatchez C, Haymaker C, Kluger H, Tetzlaff M, Gergel I, Tagliaferri M, Imperiale M, Aung S, Hoch U, Zalevsky J, Hwu P, Sznol M, Tannir N. Effect of NKTR-214 on the number and activity of CD8+ tumor infiltrating lymphocytes in patients with advanced renal cell carcinoma. Journal Of Clinical Oncology 2017, 35: 454-454. DOI: 10.1200/jco.2017.35.6_suppl.454.Peer-Reviewed Original ResearchNKTR-214T cellsTumor microenvironmentIL-2 receptor pathwayAnti-PD-1 blockadeAdvanced renal cell carcinomaImmune-related AEPatient experienced DLTPrior TKI treatmentImmune checkpoint inhibitorsT-cell receptor diversityAdvanced solid tumorsPD-1 expressionT-cell infiltratesActivity of CD8Effector T cellsFavorable safety profileRenal cell carcinomaAnti-tumor activityBaseline CD8Experienced DLTsLow TILsRECIST 1.1Checkpoint inhibitorsEffector CD8