2019
SWOG S1400D (NCT02965378), a Phase II Study of the Fibroblast Growth Factor Receptor Inhibitor AZD4547 in Previously Treated Patients With Fibroblast Growth Factor Pathway–Activated Stage IV Squamous Cell Lung Cancer (Lung-MAP Substudy)
Aggarwal C, Redman MW, Lara PN, Borghaei H, Hoffman P, Bradley JD, Newman AJ, Feldman MJ, Minichiello K, Miao J, Mack PC, Papadimitrakopoulou VA, Herbst RS, Kelly K, Gandara DR. SWOG S1400D (NCT02965378), a Phase II Study of the Fibroblast Growth Factor Receptor Inhibitor AZD4547 in Previously Treated Patients With Fibroblast Growth Factor Pathway–Activated Stage IV Squamous Cell Lung Cancer (Lung-MAP Substudy). Journal Of Thoracic Oncology 2019, 14: 1847-1852. PMID: 31195180, PMCID: PMC6901020, DOI: 10.1016/j.jtho.2019.05.041.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntineoplastic AgentsBenzamidesBiomarkers, TumorCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellFemaleFollow-Up StudiesGene AmplificationHumansLung NeoplasmsMaleMiddle AgedNeoplasm StagingPiperazinesPyrazolesReceptor, Fibroblast Growth Factor, Type 1Receptor, Fibroblast Growth Factor, Type 3Salvage TherapySurvival RateConceptsProgression-free survivalFGFR3 S249CFGFR alterationsOverall survivalPartial responseFGFR1 amplificationLung-MAPGrade 3 adverse eventsMedian progression-free survivalPlatinum-based systemic therapySolid Tumors version 1.1Squamous cell lung cancerMedian age 66 yearsFibroblast growth factor receptor inhibitorGrowth factor receptor inhibitorsFirst phase II trialGrade 4 sepsisResponse-evaluable patientsSquamous cell NSCLCUnconfirmed partial responsePhase II studyAcceptable safety profilePhase II trialResponse Evaluation CriteriaAge 66 years
2017
Phase II study of the FGFR inhibitor AZD4547 in previously treated patients with FGF pathway-activated stage IV squamous cell lung cancer (SqNSCLC): LUNG-MAP sub-study SWOG S1400D.
Aggarwal C, Redman M, Lara P, Borghaei H, Hoffman P, Bradley J, Griffin K, Miao J, Mack P, Papadimitrakopoulou V, Herbst R, Kelly K, Gandara D. Phase II study of the FGFR inhibitor AZD4547 in previously treated patients with FGF pathway-activated stage IV squamous cell lung cancer (SqNSCLC): LUNG-MAP sub-study SWOG S1400D. Journal Of Clinical Oncology 2017, 35: 9055-9055. DOI: 10.1200/jco.2017.35.15_suppl.9055.Peer-Reviewed Original ResearchOverall response rateProgression-free survivalFGFR inhibitor AZD4547Eligible ptsFGFR3 S249CStage IV squamous cell lung cancerAdequate end-organ functionMedian progression-free survivalSquamous cell lung cancerFirst phase II trialGrade 3 AEsGrade 4 sepsisGrade 5 AEsPhase II studyAcceptable safety profileEmergence of immunotherapyEnd-organ functionPhase II trialCell lung cancerDuration of responseEvaluable ptsMeasurable diseaseUnconfirmed PRII trialPrimary endpoint
2016
Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial
Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, Tsiouris AJ, Cohen J, Vortmeyer A, Jilaveanu L, Yu J, Hegde U, Speaker S, Madura M, Ralabate A, Rivera A, Rowen E, Gerrish H, Yao X, Chiang V, Kluger HM. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. The Lancet Oncology 2016, 17: 976-983. PMID: 27267608, PMCID: PMC5526047, DOI: 10.1016/s1470-2045(16)30053-5.Peer-Reviewed Original ResearchConceptsProgressive brain metastasesUntreated brain metastasesBrain metastasis responseYale Cancer CenterBrain metastasesPhase 2 trialCell lung cancerAdverse eventsMetastasis responseCancer CenterLung cancerMelanoma cohortGrade 3 colitisGrade 3 fatigueGrade 3 pneumonitisPD-1 axisAcute kidney injuryNeurological adverse eventsPD-1 inhibitorsAcceptable safety profilePD-L1 expressionSystemic immunotherapyKidney injuryPrimary endpointNSCLC cohort
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
2009
Safety of bevacizumab (B) and erlotinib (E) therapy in patients (pts) with treated brain metastases (mets) in the phase III, placebo (P)-controlled, randomized BeTa trial for pts with advanced non-small cell lung cancer (NSCLC) after failure of standard first-line chemotherapy
Otterson G, O’Connor P, Lin M, Herbst R. Safety of bevacizumab (B) and erlotinib (E) therapy in patients (pts) with treated brain metastases (mets) in the phase III, placebo (P)-controlled, randomized BeTa trial for pts with advanced non-small cell lung cancer (NSCLC) after failure of standard first-line chemotherapy. Journal Of Clinical Oncology 2009, 27: e19025-e19025. DOI: 10.1200/jco.2009.27.15_suppl.e19025.Peer-Reviewed Original ResearchNon-small cell lung cancerBrain metsBrain metastasesAdverse eventsTreatment durationAdvanced non-small cell lung cancerAdvanced stage non-small cell lung cancerStage non-small cell lung cancerEpidermal growth factor receptor-targeted therapyLung StudyNervous system adverse eventsStandard first-line chemotherapyWhole-brain radiation therapySafety of bevacizumabSubset of ptsCarboplatin/paclitaxelFirst-line chemotherapyMedian treatment durationAcceptable safety profileAdvanced NSCLC patientsBrain radiation therapyFirst-line treatmentNew safety signalsSubset of patientsReceptor-targeted therapy