2015
First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70
Owonikoko TK, Hussain A, Stadler WM, Smith DC, Kluger H, Molina AM, Gulati P, Shah A, Ahlers CM, Cardarelli PM, Cohen LJ. First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70. Cancer Chemotherapy And Pharmacology 2015, 77: 155-162. PMID: 26576779, DOI: 10.1007/s00280-015-2909-2.Peer-Reviewed Original ResearchConceptsAdverse eventsECOG performance status 0Active drug levelsGrade 3 hypersensitivityMulticenter phase IPerformance status 0Prior chemotherapy regimensFrequent adverse eventsDose-proportional increaseAdvanced ccRCCEligible patientsStatus 0Chemotherapy regimensDisease stabilizationExpansion cohortDose escalationMedian agePK analysisDrug levelsPharmacokinetic samplesB-NHLTitration designHigh doseDose levelsPatients
2014
Phase I/II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Patients With Advanced Melanoma
Ott PA, Hamid O, Pavlick AC, Kluger H, Kim KB, Boasberg PD, Simantov R, Crowley E, Green JA, Hawthorne T, Davis TA, Sznol M, Hwu P. Phase I/II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Patients With Advanced Melanoma. Journal Of Clinical Oncology 2014, 32: 3659-3666. PMID: 25267741, PMCID: PMC4879709, DOI: 10.1200/jco.2013.54.8115.Peer-Reviewed Original ResearchConceptsMaximum-tolerated doseObjective response rateGreater objective response rateGlembatumumab vedotinAdvanced melanomaGrade 3/4 treatment-related toxicitiesHuman immunoglobulin G2 monoclonal antibodyPhase I/II studyPhase II expansion cohortPromising objective response ratesEnd pointTreatment-related deathsPrimary end pointSecondary end pointsTreatment-related toxicityProgression-free survivalPhase II expansionMonomethyl auristatin E.Stable diseaseExpansion cohortII studyPartial responseDose escalationMore patientsFrequent dosing
2013
Survival and long-term follow-up of safety and response in patients (pts) with advanced melanoma (MEL) in a phase I trial of nivolumab (anti-PD-1; BMS-936558; ONO-4538).
Sznol M, Kluger H, Hodi F, McDermott D, Carvajal R, Lawrence D, Topalian S, Atkins M, Powderly J, Sharfman W, Puzanov I, Smith D, Wigginton J, Kollia G, Gupta A, Sosman J. Survival and long-term follow-up of safety and response in patients (pts) with advanced melanoma (MEL) in a phase I trial of nivolumab (anti-PD-1; BMS-936558; ONO-4538). Journal Of Clinical Oncology 2013, 31: cra9006-cra9006. DOI: 10.1200/jco.2013.31.18_suppl.cra9006.Peer-Reviewed Original ResearchPhase I trialI trialInhibitory immune checkpoint receptorsDrug-related AEsDrug-related diarrheaDrug-related pneumonitisAcceptable safety profilePhase III trialsOverall survival dataImmune checkpoint receptorsCycles of treatmentLong-term safetyMonoclonal antibody nivolumabActivated T cellsGr 3Cohort expansionECOG PSMedian OSPrior therapyIII trialsAdvanced melanomaAntibody nivolumabDose escalationPD-1Checkpoint receptorsClinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic melanoma (mM).
Hamid O, Sosman J, Lawrence D, Sullivan R, Ibrahim N, Kluger H, Boasberg P, Flaherty K, Hwu P, Ballinger M, Mokatrin A, Kowanetz M, Chen D, Hodi F. Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic melanoma (mM). Journal Of Clinical Oncology 2013, 31: 9010-9010. DOI: 10.1200/jco.2013.31.15_suppl.9010.Peer-Reviewed Original ResearchObjective response rateMM ptsPD-L1Tumor shrinkageAntitumor activityImmunotherapy-responsive diseasePD-L1 overexpressionTreatment-related deathsPD-L1 statusPD-L1 antibodiesHuman monoclonal antibodyInitial antitumor activityPt ageRECIST responseRECIST v1.1Median durationPrior surgeryPS 0Radiographic progressionSystemic therapyElevated ASTPD-1Dose escalationHistologic subtypeInitial treatment
2009
A phase I study of sunitinib in combination with sirolimus in adults with advanced refractory malignancies
Li J, Kluger H, Saif M, Murren J, Lee J, Kelly W, Rink L, Devine L, Sznol M. A phase I study of sunitinib in combination with sirolimus in adults with advanced refractory malignancies. Journal Of Clinical Oncology 2009, 27: 3554-3554. DOI: 10.1200/jco.2009.27.15_suppl.3554.Peer-Reviewed Original ResearchEarly discontinuationDose reductionDose levelsOral small-molecule inhibitorReceptor tyrosine kinasesAdvanced refractory malignanciesApparent PK interactionsHand-foot syndromeOral mTOR inhibitorDose/scheduleSoft tissue sarcomasDose of sirolimusMultiple receptor tyrosine kinasesAnti-tumor activityTumor cell proliferationDose cohortsECOG PSSunitinib doseInterstitial pneumonitisProgressive diseaseDose escalationTargeted agentsRefractory malignanciesTissue sarcomasPK interactionsPharmacokinetics (PK) of CR011-vcMMAE, an antibody-drug conjugate (ADC), in a phase (Ph) I study of patients (pts) with advanced melanoma
Sznol M, Hamid O, Hwu P, Kluger H, Hawthorne T, Crowley E, Simantov R, Pavlick A. Pharmacokinetics (PK) of CR011-vcMMAE, an antibody-drug conjugate (ADC), in a phase (Ph) I study of patients (pts) with advanced melanoma. Journal Of Clinical Oncology 2009, 27: 9063-9063. DOI: 10.1200/jco.2009.27.15_suppl.9063.Peer-Reviewed Original ResearchAntibody-drug conjugatesCR011-vcMMAETotal AbAdverse eventsMean maximum plasma concentrationNoncompartmental PK analysisCommon adverse eventsMaximum plasma concentrationEnzyme-linked immunosorbent assayQ3w scheduleQW scheduleII trialWeekly dosingAdvanced melanomaDose escalationDose scheduleCumulative dosesPK analysisPlasma concentrationsBreast cancerImmunosorbent assayPhase IPharmacokineticsPH IQ3w