2019
The Combination of MEK Inhibitor With Immunomodulatory Antibodies Targeting Programmed Death 1 and Programmed Death Ligand 1 Results in Prolonged Survival in Kras/p53-Driven Lung Cancer
Lee JW, Zhang Y, Eoh KJ, Sharma R, Sanmamed MF, Wu J, Choi J, Park HS, Iwasaki A, Kaftan E, Chen L, Papadimitrakopoulou V, Herbst RS, Koo JS. The Combination of MEK Inhibitor With Immunomodulatory Antibodies Targeting Programmed Death 1 and Programmed Death Ligand 1 Results in Prolonged Survival in Kras/p53-Driven Lung Cancer. Journal Of Thoracic Oncology 2019, 14: 1046-1060. PMID: 30771521, PMCID: PMC6542636, DOI: 10.1016/j.jtho.2019.02.004.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungAnimalsAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenDrug SynergismFemaleLung NeoplasmsMAP Kinase Kinase KinasesMiceMice, KnockoutMice, TransgenicMyeloid-Derived Suppressor CellsProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsProto-Oncogene Proteins p21(ras)PyridonesPyrimidinonesSurvival AnalysisTumor Suppressor Protein p53ConceptsImmune cell populationsLung tumorsMEK inhibitorsDeath-1Survival outcomesLung cancerL1 mAbsTumor-infiltrating immune cell populationsTumor-infiltrating immune cellsCell death ligand 1Flow cytometryLung cancer mouse modelAdenoviral Cre recombinaseAutochthonous lung tumorsImmunomodulatory monoclonal antibodiesTumor-infiltrating CD8PD-L1 expressionSingle-agent therapyTumor-bearing lungsDeath ligand 1Tumor-free miceLung cancer modelCombinatorial antitumor effectCancer mouse modelCell populations
2011
A Phase I study to assess the safety, tolerability, and pharmacokinetics of AZD4877, an intravenous Eg5 inhibitor in patients with advanced solid tumors
Infante JR, Kurzrock R, Spratlin J, Burris HA, Eckhardt SG, Li J, Wu K, Skolnik JM, Hylander-Gans L, Osmukhina A, Huszar D, Herbst RS. A Phase I study to assess the safety, tolerability, and pharmacokinetics of AZD4877, an intravenous Eg5 inhibitor in patients with advanced solid tumors. Cancer Chemotherapy And Pharmacology 2011, 69: 165-172. PMID: 21638123, DOI: 10.1007/s00280-011-1667-z.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityPrimary dose-limiting toxicityPhase IAcceptable safety profileAdvanced solid malignanciesAdvanced solid tumorsRelated adverse eventsSeverity of neutropeniaConclusionThe MTDAdverse eventsIntravenous infusionSafety profileSolid malignanciesAZD4877Intermediate doseDose reductionPart BPharmacokinetic profileDay 1Solid tumorsPart ANeutropeniaTolerabilityPatientsMTD