2022
Brief Report: Safety and Antitumor Activity of Alectinib Plus Atezolizumab From a Phase 1b Study in Advanced ALK-Positive NSCLC
Kim DW, Gadgeel S, Gettinger SN, Riely GJ, Oxnard GR, Mekhail T, Schmid P, Dowlati A, Heist RS, Wozniak AJ, Singh J, Cha E, Spahn J, Ou SI. Brief Report: Safety and Antitumor Activity of Alectinib Plus Atezolizumab From a Phase 1b Study in Advanced ALK-Positive NSCLC. JTO Clinical And Research Reports 2022, 3: 100367. PMID: 35875467, PMCID: PMC9304608, DOI: 10.1016/j.jtocrr.2022.100367.Peer-Reviewed Original ResearchTreatment-related adverse eventsPhase 1b studyAdverse eventsPositive NSCLCAntitumor activityGrade 3 treatment-related adverse eventsPreferred first-line treatment optionAdvanced ALK-positive NSCLCMedian progression-free survivalStage IIIB/IVFirst-line treatment optionDose of alectinibIIIB/IVImmune checkpoint inhibitorsMedian overall survivalObjective response rateProgression-free survivalDose-limiting toxicityALK-positive NSCLCAtezolizumab 1200Checkpoint inhibitorsStarting doseMedian durationOverall survivalCombination regimens
2021
A Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non–Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1
Weiss SA, Djureinovic D, Jessel S, Krykbaeva I, Zhang L, Jilaveanu L, Ralabate A, Johnson B, Levit NS, Anderson G, Zelterman D, Wei W, Mahajan A, Trifan O, Bosenberg M, Kaech SM, Perry CJ, Damsky W, Gettinger S, Sznol M, Hurwitz M, Kluger HM. A Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non–Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1. Clinical Cancer Research 2021, 27: 4757-4767. PMID: 34140403, PMCID: PMC9236708, DOI: 10.1158/1078-0432.ccr-21-0903.Peer-Reviewed Original ResearchConceptsAnti-PD-1/PD-L1Non-small cell lung cancerCell lung cancerRenal cell carcinomaPD-L1Lung cancerDisease progressionCommon treatment-related adverse eventsPD-1/PD-L1 inhibitorsTreatment-related adverse eventsPhase 2 doseSubstantial clinical challengeUnconfirmed partial responseDose-limiting toxicityPD-L1 inhibitorsPhase I trialDose-escalation designPro-inflammatory cytokinesMultiple tumor typesAsymptomatic elevationStable diseaseIntolerable toxicityAdverse eventsMedian durationPartial responseA Dose-finding Study Followed by a Phase II Randomized, Placebo-controlled Trial of Chemoradiotherapy With or Without Veliparib in Stage III Non–small-cell Lung Cancer: SWOG 1206 (8811)
Argiris A, Miao J, Cristea MC, Chen AM, Sands JM, Decker RH, Gettinger SN, Daly ME, Faller BA, Albain KS, Yanagihara RH, Garland LL, Byers LA, Wang D, Koczywas M, Redman MW, Kelly K, Gandara DR. A Dose-finding Study Followed by a Phase II Randomized, Placebo-controlled Trial of Chemoradiotherapy With or Without Veliparib in Stage III Non–small-cell Lung Cancer: SWOG 1206 (8811). Clinical Lung Cancer 2021, 22: 313-323.e1. PMID: 33745865, PMCID: PMC8562492, DOI: 10.1016/j.cllc.2021.02.009.Peer-Reviewed Original ResearchConceptsProgression-free survivalDose-limiting toxicityGrade 3 esophagitisPhase II partCell lung cancerLung cancerStage IIIPARP inhibitorsConcurrent weekly carboplatinEarly study closurePhase II RandomizedTrial of chemoradiotherapyDose-finding studyPhase I partStandard of careAdjuvant immunotherapyConsolidation carboplatinEligible patientsVeliparib doseWeekly carboplatinThoracic radiotherapyOverall survivalPlacebo armStudy closurePredictive biomarkers
2020
Bempegaldesleukin (NKTR-214) plus Nivolumab in Patients with Advanced Solid Tumors: Phase I Dose-Escalation Study of Safety, Efficacy, and Immune Activation (PIVOT-02)
Diab A, Tannir NM, Bentebibel SE, Hwu P, Papadimitrakopoulou V, Haymaker C, Kluger HM, Gettinger SN, Sznol M, Tykodi SS, Curti BD, Tagliaferri MA, Zalevsky J, Hannah AL, Hoch U, Aung S, Fanton C, Rizwan A, Iacucci E, Liao Y, Bernatchez C, Hurwitz ME, Cho DC. Bempegaldesleukin (NKTR-214) plus Nivolumab in Patients with Advanced Solid Tumors: Phase I Dose-Escalation Study of Safety, Efficacy, and Immune Activation (PIVOT-02). Cancer Discovery 2020, 10: 1158-1173. PMID: 32439653, DOI: 10.1158/2159-8290.cd-19-1510.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCarcinoma, Renal CellFemaleGene Expression Regulation, NeoplasticHumansImmune Checkpoint InhibitorsImmunotherapyInterleukin-2Kidney NeoplasmsLung NeoplasmsLymphocyte CountLymphocytes, Tumor-InfiltratingMaleMelanomaMiddle AgedNivolumabPolyethylene GlycolsProgrammed Cell Death 1 ReceptorTreatment OutcomeYoung AdultConceptsTreatment-related adverse eventsAdvanced solid tumorsPD-L1 statusSolid tumorsGrade 3/4 treatment-related adverse eventsPD-1/PD-L1 blockadeCommon treatment-related adverse eventsPhase I dose-escalation trialPoor prognostic risk factorsTotal objective response rateI dose-escalation studyI dose-escalation trialLongitudinal tumor biopsiesPD-L1 blockadeT-cell enhancementTreatment-related deathsObjective response ratePhase II doseDose-escalation studyDose-escalation trialDose-limiting toxicityFlu-like symptomsPrognostic risk factorsTumor-infiltrating lymphocytesCytotoxicity of CD8Phase 1 study of epacadostat in combination with atezolizumab for patients with previously treated advanced nonsmall cell lung cancer
Hellmann MD, Gettinger S, Chow LQM, Gordon M, Awad MM, Cha E, Gong X, Zhou G, Walker C, Leopold L, Heist RS. Phase 1 study of epacadostat in combination with atezolizumab for patients with previously treated advanced nonsmall cell lung cancer. International Journal Of Cancer 2020, 147: 1963-1969. PMID: 32141617, PMCID: PMC7496129, DOI: 10.1002/ijc.32951.Peer-Reviewed Original ResearchConceptsNonsmall cell lung cancerTreatment-related adverse eventsDose-limiting toxicityCell lung cancerAdverse eventsLung cancerStage IIIB/IV nonsmall cell lung cancerFatal treatment-related adverse eventsAdvanced nonsmall cell lung cancerCell death ligand 1Grade 3 dehydrationGrade 3 hyponatremiaGrade 3/4 eventsPhase 1 studyPlatinum-based chemotherapyDeath ligand 1Dose of treatmentAutoimmune encephalitisEligible patientsIntravenous atezolizumabStable diseasePrimary endpointPartial responsePrior linesIDO expression
2017
A phase Ib/II study of cabozantinib (XL184) with or without erlotinib in patients with non-small cell lung cancer
Wakelee HA, Gettinger S, Engelman J, Jänne PA, West H, Subramaniam DS, Leach J, Wax M, Yaron Y, Miles DR, Lara PN. A phase Ib/II study of cabozantinib (XL184) with or without erlotinib in patients with non-small cell lung cancer. Cancer Chemotherapy And Pharmacology 2017, 79: 923-932. PMID: 28352985, PMCID: PMC5403837, DOI: 10.1007/s00280-017-3283-z.Peer-Reviewed Original ResearchConceptsObjective response ratePhase Ib/II studyII studyPhase INon-small cell lung cancerFrequent dose-limiting toxicityPhase IIDose of cabozantinibDose-limiting toxicityResultsSixty-four patientsCell lung cancerMulti-kinase inhibitorProgressive NSCLCStable diseaseCombination armPartial responseFrequent AEsErlotinib treatmentLung cancerEGFR mutationsErlotinib pharmacokineticsCabozantinibPatientsPrimary objectiveResponse rate
2016
Nivolumab in Combination With Platinum‐Based Doublet Chemotherapy for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer
Rizvi NA, Hellmann MD, Brahmer JR, Juergens RA, Borghaei H, Gettinger S, Chow LQ, Gerber DE, Laurie SA, Goldman JW, Shepherd FA, Chen AC, Shen Y, Nathan FE, Harbison CT, Antonia S. Nivolumab in Combination With Platinum‐Based Doublet Chemotherapy for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2016, 34: 2969-2979. PMID: 27354481, PMCID: PMC5569693, DOI: 10.1200/jco.2016.66.9861.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenCarboplatinCarcinoma, Non-Small-Cell LungCisplatinCohort StudiesDeoxycytidineDisease-Free SurvivalDose-Response Relationship, DrugErbB ReceptorsFemaleGemcitabineHumansLung NeoplasmsMaleMiddle AgedNivolumabPemetrexedProto-Oncogene Proteins p21(ras)Survival RateConceptsPlatinum-based doublet chemotherapyTreatment-related adverse eventsProgression-free survival ratesDeath ligand 1 (PD-L1) expressionObjective response ratePercent of patientsLigand 1 expressionAdverse eventsPaclitaxel-carboplatinDoublet chemotherapyOverall survivalOS ratesLung cancerDeath-1 immune checkpoint inhibitor antibodyAdvanced non-small cell lung cancerResponse rateSurvival rateNon-small cell lung cancerImmune checkpoint inhibitor antibodyCheckpoint inhibitor antibodyEfficacy of nivolumabPaclitaxel-carboplatin groupDose-limiting toxicityCurrent standard therapyWeeks of treatment
2015
Phase 1b study of the mammalian target of rapamycin inhibitor sirolimus in combination with nanoparticle albumin–bound paclitaxel in patients with advanced solid tumors
Abu-Khalaf MM, Baumgart MA, Gettinger SN, Doddamane I, Tuck DP, Hou S, Chen N, Sullivan C, Lezon-Geyda K, Zelterman D, Hatzis C, Deshpande H, Digiovanna MP, Azodi M, Schwartz PE, Harris LN. Phase 1b study of the mammalian target of rapamycin inhibitor sirolimus in combination with nanoparticle albumin–bound paclitaxel in patients with advanced solid tumors. Cancer 2015, 121: 1817-1826. PMID: 25649370, DOI: 10.1002/cncr.29254.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityIntravenous nab-paclitaxelPhase 1b studyAdvanced solid tumorsNab-paclitaxelFDG activityDay 1Solid tumorsNanoparticle albumin-bound paclitaxelMammalian targetWeekly oral doseAcceptable safety profileRapamycin inhibitor sirolimusAlbumin-bound paclitaxelClinical trial endpointsExploratory gene expression analysisPositron emission tomographyStable diseaseTaxane therapyPartial responseWeekly doseComplete responseOral sirolimusPharmacodynamic assessmentOral dose
2013
Phase I Study of the Hedgehog Pathway Inhibitor IPI-926 in Adult Patients with Solid Tumors
Jimeno A, Weiss GJ, Miller WH, Gettinger S, Eigl BJ, Chang AL, Dunbar J, Devens S, Faia K, Skliris G, Kutok J, Lewis KD, Tibes R, Sharfman WH, Ross RW, Rudin CM. Phase I Study of the Hedgehog Pathway Inhibitor IPI-926 in Adult Patients with Solid Tumors. Clinical Cancer Research 2013, 19: 2766-2774. PMID: 23575478, PMCID: PMC3694426, DOI: 10.1158/1078-0432.ccr-12-3654.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAlanine TransaminaseAlopeciaArea Under CurveAspartate AminotransferasesDose-Response Relationship, DrugDrug Administration ScheduleFatigueFemaleFollow-Up StudiesHedgehog ProteinsHumansMaleMetabolic Clearance RateMiddle AgedNauseaNeoplasmsSignal TransductionSpasmTreatment OutcomeVeratrum AlkaloidsConceptsBasal cell carcinomaDose-limiting toxicityInhibitor-naïve patientsIPI-926Alanine aminotransferaseSolid tumorsAspartate aminotransferaseAccelerated titration scheduleDose-escalation cohortsPhase II doseResponse Evaluation CriteriaSingle-agent activityHuman phase ISolid Tumors assessmentHematologic toxicityStarting doseAdult patientsStandard therapyMuscle spasmTitration scheduleReversible elevationCell carcinomaQD dosingTumor assessmentPharmacokinetic profile
2012
A phase I study of BMS-936558 in combination with gemcitabine/cisplatin, pemetrexed/cisplatin, or carboplatin/paclitaxel in patients with treatment-naive, stage IIIB/IV non-small-cell lung cancer.
Gettinger S, Rizvi N, Shepherd F, Chow L, Laurie S, Spigel D, Sbar E, Shen Y, Brahmer J. A phase I study of BMS-936558 in combination with gemcitabine/cisplatin, pemetrexed/cisplatin, or carboplatin/paclitaxel in patients with treatment-naive, stage IIIB/IV non-small-cell lung cancer. Journal Of Clinical Oncology 2012, 30: tps2615-tps2615. DOI: 10.1200/jco.2012.30.15_suppl.tps2615.Peer-Reviewed Original ResearchBMS-936558Cell lung cancerAdverse eventsTreatment armsLung cancerDisease progressionAnti-PD-1 monoclonal antibodyStage IIIB/IV NSCLCPlatinum-based doublet chemotherapyStage IIIB/IVImpressive tumor responsesCarboplatin/paclitaxelDisease control rateIIIB/IVFirst-line standardPD-1 expressionSerious adverse eventsDose-limiting toxicityGemcitabine/cisplatinPhase 1 studyPlatinum-based chemotherapyPhase 1 trialCancer-related mortalityOverall response rateWithdrawal of consent
2010
Phase I/II Study of Inhaled Doxorubicin Combined with Platinum-Based Therapy for Advanced Non–Small Cell Lung Cancer
Otterson GA, Villalona-Calero MA, Hicks W, Pan X, Ellerton JA, Gettinger SN, Murren JR. Phase I/II Study of Inhaled Doxorubicin Combined with Platinum-Based Therapy for Advanced Non–Small Cell Lung Cancer. Clinical Cancer Research 2010, 16: 2466-2473. PMID: 20371682, PMCID: PMC4262532, DOI: 10.1158/1078-0432.ccr-09-3015.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdministration, InhalationAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Large CellCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellCisplatinDocetaxelDoxorubicinFemaleHumansLung NeoplasmsMaleMaximum Tolerated DoseMiddle AgedSurvival RateTaxoidsTreatment OutcomeConceptsNon-small cell lung cancerCell lung cancerAdvanced non-small cell lung cancerDose-limiting toxicityLung cancerEvaluable patientsPhase I/II studyDose level 1Phase II dosePulmonary function testsDoses of cisplatinStable diseaseII studyProgressive diseaseExpiratory volumePulmonary functionFunction testsVital capacityPulmonary toxicityAdequate organPatientsCancerLevel 1Phase ILevel 2