2024
Pooled analysis by best confirmed response to trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2+ metastatic breast cancer (mBC) from DESTINY-Breast-01, -02, and -03.
Saura C, Cortés J, Modi S, Kim S, Hamilton E, Hurvitz S, Krop I, Curigliano G, Iwata H, Im S, Herbolsheimer P, Karnoub M, Gambhire D, Egorov A, Andre F. Pooled analysis by best confirmed response to trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2+ metastatic breast cancer (mBC) from DESTINY-Breast-01, -02, and -03. Journal Of Clinical Oncology 2024, 42: 1023-1023. DOI: 10.1200/jco.2024.42.16_suppl.1023.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsHER2+ metastatic breast cancerProgression-free survivalMetastatic breast cancerComplete responsePartial responseT-DXdOverall survivalPooled analysisInterstitial lung disease (ILD)/pneumonitisStable disease (SD)/progressive diseaseProlonged progression-free survivalDuration of responseIndependent central reviewNumerically lower ratesLonger treatment durationMetastatic settingRECIST v1.1Trastuzumab deruxtecanOS outcomesCentral reviewAdverse eventsBreast cancerTreatment durationDrug-related
2022
Trastuzumab Deruxtecan in HER2-Positive Metastatic Breast Cancer Patients with Brain Metastases: A DESTINY-Breast01 Subgroup Analysis
Jerusalem G, Park YH, Yamashita T, Hurvitz S, Modi S, Andre F, Krop I, Farré X, You B, Saura C, Kim S, Osborne C, Murthy R, Gianni L, Takano T, Liu Y, Cathcart J, Lee C, Perrin C. Trastuzumab Deruxtecan in HER2-Positive Metastatic Breast Cancer Patients with Brain Metastases: A DESTINY-Breast01 Subgroup Analysis. Cancer Discovery 2022, 12: 2754-2762. PMID: 36255231, PMCID: PMC9716244, DOI: 10.1158/2159-8290.cd-22-0837.Peer-Reviewed Original ResearchConceptsMedian progression-free survivalMetastatic breast cancerHER2-positive metastatic breast cancerBrain metastasesT-DXdTrastuzumab deruxtecanBreast cancerHER2-positive metastatic breast cancer patientsMetastatic breast cancer patientsDurable clinical activityObjective response rateProgression-free survivalBreast cancer patientsLimited treatment optionsPopulation warrants further investigationBest percentage changeWarrants further investigationIntracranial progressionStable diseasePartial responseComplete responseDurable efficacySafety profileTherapeutic optionsTreatment optionsPhase II Study of Taselisib in PIK3CA-Mutated Solid Tumors Other Than Breast and Squamous Lung Cancer: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol I
Krop IE, Jegede OA, Grilley-Olson JE, Lauring JD, Mitchell EP, Zwiebel JA, Gray RJ, Wang V, McShane LM, Rubinstein LV, Patton D, Williams PM, Hamilton SR, Kono SA, Ford JM, Garcia AA, Sui XD, Siegel RD, Slomovitz BM, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. Phase II Study of Taselisib in PIK3CA-Mutated Solid Tumors Other Than Breast and Squamous Lung Cancer: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol I. JCO Precision Oncology 2022, 6: e2100424. PMID: 35138919, PMCID: PMC8865530, DOI: 10.1200/po.21.00424.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall survivalSix-month progression-free survivalSolid tumorsMedian progression-free survivalSix-month overall survivalEnd pointSquamous cell lung carcinomaNational Cancer Institute-Molecular AnalysisMedian overall survivalObjective response ratePhase II studyPrimary end pointSecondary end pointsCell lung carcinomaSquamous lung cancerMutant breast cancerCommon toxicitiesEligible patientsProtocol therapyUnacceptable toxicityII studyPartial responseAdvanced cancerClinical outcomes
2020
Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer
Garrido-Castro AC, Saura C, Barroso-Sousa R, Guo H, Ciruelos E, Bermejo B, Gavilá J, Serra V, Prat A, Paré L, Céliz P, Villagrasa P, Li Y, Savoie J, Xu Z, Arteaga CL, Krop IE, Solit DB, Mills GB, Cantley LC, Winer EP, Lin NU, Rodon J. Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer. Breast Cancer Research 2020, 22: 120. PMID: 33138866, PMCID: PMC7607628, DOI: 10.1186/s13058-020-01354-y.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAminopyridinesAntineoplastic Combined Chemotherapy ProtocolsClass I Phosphatidylinositol 3-KinasesDisease ProgressionFemaleHigh-Throughput Nucleotide SequencingHumansMiddle AgedMorpholinesNeoplasm MetastasisPatient SafetyProtein Kinase InhibitorsProteomicsResponse Evaluation Criteria in Solid TumorsSurvival RateTreatment OutcomeTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerProgression-free survivalPan-class I PI3K inhibitorMetastatic triple-negative breast cancerStable diseasePhase 2 studyBreast cancerOverall survivalPI3K inhibitorsPI3K pathwayPartial responseComplete responseClinical benefitSingle-arm phase 2 studyTriple-negative metastatic breast cancerMedian progression-free survivalK inhibitorsClinical benefit rateEfficacy of buparlisibK pathwayFrequent adverse eventsMedian overall survivalPercent of patientsMetastatic breast cancerSubset of patients
2019
First‐in‐human, phase I study of PF‐06647263, an anti‐EFNA4 calicheamicin antibody–drug conjugate, in patients with advanced solid tumors
Garrido‐Laguna I, Krop I, Burris HA, Hamilton E, Braiteh F, Weise AM, Abu‐Khalaf M, Werner TL, Pirie‐Shepherd S, Zopf CJ, Lakshminarayanan M, Holland JS, Baffa R, Hong DS. First‐in‐human, phase I study of PF‐06647263, an anti‐EFNA4 calicheamicin antibody–drug conjugate, in patients with advanced solid tumors. International Journal Of Cancer 2019, 145: 1798-1808. PMID: 30680712, PMCID: PMC6875752, DOI: 10.1002/ijc.32154.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerAdvanced solid tumorsTumor responseSolid tumorsMetastatic triple-negative breast cancerPhase IPhase 2 doseAntitumor activityHuman xenograft tumor modelsAvailable standard therapiesDose-related mannerLimited antitumor activityXenograft tumor modelCommon AEsStable diseaseManageable safetyPartial responsePotent antitumor activityStandard therapyToxicity probability interval methodOvarian cancerBreast cancerPatientsRP2DTumor model
2018
Phase III study of taselisib (GDC-0032) + fulvestrant (FULV) v FULV in patients (pts) with estrogen receptor (ER)-positive, PIK3CA -mutant (MUT), locally advanced or metastatic breast cancer (MBC): Primary analysis from SANDPIPER.
Baselga J, Dent S, Cortés J, Im Y, Diéras V, Harbeck N, Krop I, Verma S, Wilson T, Jin H, Wang L, Schimmoller F, Hsu J, He J, DeLaurentiis M, Drullinsky P, Jacot W. Phase III study of taselisib (GDC-0032) + fulvestrant (FULV) v FULV in patients (pts) with estrogen receptor (ER)-positive, PIK3CA -mutant (MUT), locally advanced or metastatic breast cancer (MBC): Primary analysis from SANDPIPER. Journal Of Clinical Oncology 2018, 36: lba1006-lba1006. DOI: 10.1200/jco.2018.36.18_suppl.lba1006.Peer-Reviewed Original ResearchInvestigator-assessed progression-free survivalMetastatic breast cancerClinical benefit rateObjective response rateOverall survivalBlinded independent central reviewProgression-free survivalIndependent central reviewDose of treatmentSelective PI3K inhibitorBC cell linesPI3K inhibitorsTreat populationPrimary endpointSecondary endpointsAdverse eventsObjective responsePartial responseVisceral diseaseDisease recurrenceEndocrine sensitivityCentral reviewSafety profileAromatase inhibitorsBenefit ratePhase 1/1b dose escalation and expansion study of BEZ235, a dual PI3K/mTOR inhibitor, in patients with advanced solid tumors including patients with advanced breast cancer
Rodon J, Pérez-Fidalgo A, Krop IE, Burris H, Guerrero-Zotano A, Britten CD, Becerra C, Schellens J, Richards DA, Schuler M, Abu-Khalaf M, Johnson FM, Ranson M, Edenfield J, Silva AP, Hackl W, Quadt C, Demanse D, Duval V, Baselga J. Phase 1/1b dose escalation and expansion study of BEZ235, a dual PI3K/mTOR inhibitor, in patients with advanced solid tumors including patients with advanced breast cancer. Cancer Chemotherapy And Pharmacology 2018, 82: 285-298. PMID: 29882016, PMCID: PMC6286256, DOI: 10.1007/s00280-018-3610-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsDose-Response Relationship, DrugDrug CompoundingFemaleHumansImidazolesMaleMiddle AgedNeoplasmsPhosphoinositide-3 Kinase InhibitorsQuinolinesTOR Serine-Threonine KinasesTrastuzumabConceptsAdvanced breast cancerSingle agentBreast cancerSolid tumorsHigh dosesPhase I/IbEnd pointDual PI3K/mTOR inhibitorContinuous daily scheduleDose-escalation partMost frequent AEsOpen-label studyPrimary end pointSecondary end pointsAdvanced solid tumorsPI3K/mTOR inhibitorCombination cohortConclusionsThe MTDGastrointestinal AEsPartial responseDose escalationFrequent AEsOral inhibitorResultsOne hundredLow dose
2017
A phase I study of PF-06647263, a novel EFNA4-ADC, in patients with metastatic triple negative breast cancer.
Garrido-Laguna I, Krop I, Burris H, Hamilton E, Braiteh F, Weise A, Abu-Khalaf M, Zopf C, Lakshminarayanan M, Holland J, Baffa R, Hong D, Hassan R. A phase I study of PF-06647263, a novel EFNA4-ADC, in patients with metastatic triple negative breast cancer. Journal Of Clinical Oncology 2017, 35: 2511-2511. DOI: 10.1200/jco.2017.35.15_suppl.2511.Peer-Reviewed Original ResearchTriple-negative breast cancerAdverse eventsNegative breast cancerExpansion cohortPartial responseBreast cancerMetastatic triple-negative breast cancerAnti-drug antibody developmentCommon adverse eventsDuration of treatmentAnti-tumor activityVivo preclinical studiesQ3w scheduleQW scheduleRECIST responseAdvanced malignanciesMucosal inflammationObjective responseDose escalationTNBC patientsTumor regressionTNBC modelsPreclinical studiesCommon treatmentPK dataA phase II study of eribulin mesylate in combination with trastuzumab and pertuzumab in patients (pts) with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC).
Luis I, Guo H, Barry W, Krop I, Wagle N, Lowe A, Gore D, Andrews C, Osmani W, Isakoff S, Tung N, Winer E, Lin N, Freedman R. A phase II study of eribulin mesylate in combination with trastuzumab and pertuzumab in patients (pts) with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC). Journal Of Clinical Oncology 2017, 35: 1034-1034. DOI: 10.1200/jco.2017.35.15_suppl.1034.Peer-Reviewed Original ResearchMetastatic breast cancerOverall response ratePhase II studyStable diseasePertuzumab exposureAdverse eventsII studyCohort AHuman epidermal growth factor receptorActivity of eribulinDose of eribulinFrequent grade 3First-line settingMost adverse eventsAnti-HER2 therapyCorrelative studiesEpidermal growth factor receptorCell-free DNAGrowth factor receptorHematologic toxicityCohort studyOverall survivalPartial responseCohort BSingle centerSANDPIPER: Phase III study of the PI3-kinase (PI3K) inhibitor taselisib (GDC-0032) plus fulvestrant in patients (pts) with estrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer (BC) enriched for pts with PIK3CA- mutant tumors.
Baselga J, Cortés J, DeLaurentiis M, Dent S, Diéras V, Harbeck N, Hsu J, Jin H, Schimmoller F, Wilson T, Im Y, Jacot W, Krop I, Verma S. SANDPIPER: Phase III study of the PI3-kinase (PI3K) inhibitor taselisib (GDC-0032) plus fulvestrant in patients (pts) with estrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer (BC) enriched for pts with PIK3CA- mutant tumors. Journal Of Clinical Oncology 2017, 35: tps1119-tps1119. DOI: 10.1200/jco.2017.35.15_suppl.tps1119.Peer-Reviewed Original ResearchPIK3CA-mutant tumorsMetastatic breast cancerBreast cancerPIK3CA mutationsInvestigator-assessed progression-free survivalHER2-negative breast tumorsClinical benefit rateObjective response ratePrimary efficacy endpointProgression-free survivalPatient-reported outcomesAromatase inhibitor treatmentSelective PI3K inhibitorFrequent genomic alterationsProliferation of tumorsBC cell linesPIK3CA mutant breast cancersPI3K inhibitorsEfficacy endpointObjective responseOverall survivalPartial responseVisceral diseaseDisease recurrenceEndocrine sensitivity
2015
Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer
Tolaney SM, Tan S, Guo H, Barry W, Van Allen E, Wagle N, Brock J, Larrabee K, Paweletz C, Ivanova E, Janne P, Overmoyer B, Wright JJ, Shapiro GI, Winer EP, Krop IE. Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer. Investigational New Drugs 2015, 33: 1108-1114. PMID: 26123926, PMCID: PMC4608248, DOI: 10.1007/s10637-015-0269-8.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerTriple-negative breast cancerPhase 2 studyProgression-free survivalBreast cancerPartial responseSingle-arm phase 2 studyResults 22 patientsPhase II studyDaily oral dosingOverall response rateRecent preclinical dataMechanism of actionTivantinib monotherapyMetastatic settingAdverse eventsII studyMethods PatientsPrior linesPreclinical dataOral dosingTivantinibPatientsMET expressionResponse rate
2014
Phase I/II study of pilaralisib (SAR245408) in combination with trastuzumab or trastuzumab plus paclitaxel in trastuzumab-refractory HER2-positive metastatic breast cancer
Tolaney S, Burris H, Gartner E, Mayer IA, Saura C, Maurer M, Ciruelos E, Garcia AA, Campana F, Wu B, Xu Y, Jiang J, Winer E, Krop I. Phase I/II study of pilaralisib (SAR245408) in combination with trastuzumab or trastuzumab plus paclitaxel in trastuzumab-refractory HER2-positive metastatic breast cancer. Breast Cancer Research And Treatment 2014, 149: 151-161. PMID: 25537644, DOI: 10.1007/s10549-014-3248-4.Peer-Reviewed Original ResearchConceptsHER2-positive metastatic breast cancerMetastatic breast cancerAdverse eventsBreast cancerArm 2Arm 1Phase I/II dose-escalation studyMetastatic HER2-positive breast cancerPhase I/II studyTreatment-related adverse eventsHER2-positive breast cancerTreatment-related gradeAcceptable safety profileDose-escalation studyDose-limiting toxicityDose-escalation designPan-class IEvaluable patientsPaclitaxel armPrior taxanePrior trastuzumabErythematous rashII studyPartial responsePeripheral neuropathy
2013
Phase II trial of carboplatin (C) and bevacizumab (BEV) in patients (pts) with breast cancer brain metastases (BCBM).
Lin N, Gelman R, Younger W, Sohl J, Freedman R, Sorensen A, Bullitt E, Harris G, Morganstern D, Schneider B, Krop I, Winer E. Phase II trial of carboplatin (C) and bevacizumab (BEV) in patients (pts) with breast cancer brain metastases (BCBM). Journal Of Clinical Oncology 2013, 31: 513-513. DOI: 10.1200/jco.2013.31.15_suppl.513.Peer-Reviewed Original ResearchBreast cancer brain metastasesCNS responseDay 1CNS objective response rateNon-target lesionsObjective response rateAnti-edema effectCancer brain metastasesPhase II trialProgressive neurologic signsStandard brain MRINon-CNS diseasesMultiple tumor typesPrior lapatinibPrior trastuzumabRECIST 1.0Steroid dosePrimary endpointProtocol therapyBrain metastasesFirst doseII trialCNS lesionsOverall survivalPartial response
2012
A phase I/IB dose-escalation study of BEZ235 in combination with trastuzumab in patients with PI3-kinase or PTEN altered HER2+ metastatic breast cancer.
Krop I, Saura C, Rodon Ahnert J, Becerra C, Britten C, Isakoff S, Demanse D, Hackl W, Quadt C, Silva A, Burris H, Abu-Khalaf M, Baselga J. A phase I/IB dose-escalation study of BEZ235 in combination with trastuzumab in patients with PI3-kinase or PTEN altered HER2+ metastatic breast cancer. Journal Of Clinical Oncology 2012, 30: 508-508. DOI: 10.1200/jco.2012.30.15_suppl.508.Peer-Reviewed Original ResearchMetastatic breast cancerPI3K pathway alterationsBreast cancerG3 nauseaResistant HER2Disease stabilizationPathway alterationsPI3K/AKT/mTOR pathwayAcceptable safety profileDose-escalation studyAdvanced solid tumorsAKT/mTOR pathwayBreast cancer modelLogistic regression modelsPI3K pathwayG3 fatigueObserved DLTsBrain metastasesPartial responseSkin rashAdverse eventsLiver metastasesDose escalationSafety profileDose levels
2011
Phase I/II Study of Trastuzumab in Combination With Everolimus (RAD001) in Patients With HER2-Overexpressing Metastatic Breast Cancer Who Progressed on Trastuzumab-Based Therapy
Morrow PK, Wulf GM, Ensor J, Booser DJ, Moore JA, Flores PR, Xiong Y, Zhang S, Krop IE, Winer EP, Kindelberger DW, Coviello J, Sahin AA, Nuñez R, Hortobagyi GN, Yu D, Esteva FJ. Phase I/II Study of Trastuzumab in Combination With Everolimus (RAD001) in Patients With HER2-Overexpressing Metastatic Breast Cancer Who Progressed on Trastuzumab-Based Therapy. Journal Of Clinical Oncology 2011, 29: 3126-3132. PMID: 21730275, PMCID: PMC3157979, DOI: 10.1200/jco.2010.32.2321.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsDisease-Free SurvivalEverolimusFemaleHumansImmunohistochemistryKaplan-Meier EstimateMiddle AgedNeoplasm MetastasisPTEN PhosphohydrolaseReceptor, ErbB-2Salvage TherapySirolimusTOR Serine-Threonine KinasesTrastuzumabConceptsHER2-overexpressing metastatic breast cancerMetastatic breast cancerProgression-free survivalCombination of everolimusTrastuzumab-based therapyPTEN lossBreast cancerPhase I/II studyMedian progression-free survivalDana-Farber Cancer InstituteTexas MD Anderson Cancer CenterMD Anderson Cancer CenterBeth Israel Deaconess Medical CenterClinical benefit ratePersistent stable diseaseAnderson Cancer CenterDownstream mammalian targetDaily everolimusNonhematologic toxicityStable diseaseII studyOverall survivalPartial responseHER2 overexpressingClinical benefitResponses to subsequent anti-HER2 therapy after treatment with trastuzumab-DM1 in women with HER2-positive metastatic breast cancer
Olson EM, Lin NU, DiPiro PJ, Najita JS, Krop IE, Winer EP, Burstein HJ. Responses to subsequent anti-HER2 therapy after treatment with trastuzumab-DM1 in women with HER2-positive metastatic breast cancer. Annals Of Oncology 2011, 23: 93-97. PMID: 21531783, PMCID: PMC3276325, DOI: 10.1093/annonc/mdr061.Peer-Reviewed Original ResearchConceptsAnti-HER2 therapyMetastatic breast cancerHER2-positive MBC patientsT-DM1MBC patientsBreast cancerHER2-positive metastatic breast cancerSingle-agent T-DM1Positive metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Blinded radiology reviewAnti-HER2 agentsGrowth factor receptor 2Kaplan-Meier estimatesFurther clinical benefitFactor receptor 2Protocol therapyMedian durationFurther therapyPartial responseRadiology reviewClinical benefitSubsequent linesMetastatic therapy
2009
Quantitative assessment of HER2 status and correlation with efficacy for patients (pts) with metastatic breast cancer (MBC) in a phase II study of trastuzumab-DM1 (T-DM1)
Krop I, Burris H, Rugo H, O'Shaughnessy J, Vogel C, Amler L, Strauss A, Wong E, Klencke B, Pippen J. Quantitative assessment of HER2 status and correlation with efficacy for patients (pts) with metastatic breast cancer (MBC) in a phase II study of trastuzumab-DM1 (T-DM1). Journal Of Clinical Oncology 2009, 27: 1003-1003. DOI: 10.1200/jco.2009.27.15_suppl.1003.Peer-Reviewed Original ResearchMetastatic breast cancerEnzyme-linked immunosorbent assayPhase II studyPartial responseTrastuzumab-DM1II studyQRT-PCRGood responseSingle-arm studyT-DM1 therapyCentral laboratory testingAdditional diagnostic markerReal-time polymerase chain reactionQuantitative real-time polymerase chain reactionAnti-microtubule agentsMedian 4.4Metastatic settingCorrelation of responseHER2 statusPolymerase chain reactionBreast cancerECD levelsMedian levelsResponse ratePT serumA phase II study of ixabepilone plus trastuzumab for metastatic HER2-positive breast cancer.
Tolaney S, Najita J, Chen W, Savoie J, Fornier M, Krop I, Winer E, Bunnell C. A phase II study of ixabepilone plus trastuzumab for metastatic HER2-positive breast cancer. Cancer Research 2009, 69: 3137. DOI: 10.1158/0008-5472.sabcs-3137.Peer-Reviewed Original ResearchMetastatic HER2-positive breast cancerHER2-positive breast cancerCombination of ixabepiloneBreast cancerPartial responseCohort 1Response rateMetastatic diseaseCohort 2Clinical benefit rateHigher cardiac toxicityRefractory breast cancerSubsequent-line therapyTrastuzumab-containing regimensCycles of therapyPhase II studyTreatment-related toxicityCohort of patientsEncouraging response ratesMetastatic breast cancerSame treatment regimenOverall response ratePrior chemotherapyStable diseaseElevated transaminasesA phase I study of weekly dosing of trastuzumab-DM1 (T-DM1) in patients with advanced HER2+ breast cancer.
Krop I, Mita M, Burris H, Birkner M, Girish S, Tibbitts J, Holden S, Lutzker S, Modi S. A phase I study of weekly dosing of trastuzumab-DM1 (T-DM1) in patients with advanced HER2+ breast cancer. Cancer Research 2009, 69: 3136. DOI: 10.1158/0008-5472.sabcs-3136.Peer-Reviewed Original ResearchTrastuzumab-DM1Advanced HER2Antibody-drug conjugatesBreast cancerChemotherapy regimenCycle 1 day 1HER2 antibody-drug conjugatesFirst antibody-drug conjugatePhase IActivity of trastuzumabGrade 4 thrombocytopeniaReversible transaminase elevationT-DM1 exposureDose-escalation studyPhase II trialMeasurable diseaseQ3W dosingTransaminase elevationEscalation studyII trialPartial responseWeekly dosingCardiac toxicityTumor responseClinical trials
2007
A phase I study of trastuzumab-MCC-DM1 (T-DM1), a first-in-class HER2 antibody-drug conjugate (ADC), in patients (pts) with HER2+ metastatic breast cancer (BC)
Beeram M, Krop I, Modi S, Tolcher A, Rabbee N, Girish S, Tibbitts J, Holden S, Lutzker S, Burris H. A phase I study of trastuzumab-MCC-DM1 (T-DM1), a first-in-class HER2 antibody-drug conjugate (ADC), in patients (pts) with HER2+ metastatic breast cancer (BC). Journal Of Clinical Oncology 2007, 25: 1042-1042. DOI: 10.1200/jco.2007.25.18_suppl.1042.Peer-Reviewed Original ResearchAntibody-drug conjugatesMetastatic breast cancerAdverse eventsT-DM1Breast cancerDose levelsHER2 antibody-drug conjugatesFirst antibody-drug conjugatePhase IOngoing partial responsePrincipal adverse eventsReversible transaminase elevationT-DM1 pharmacokineticsObjective tumor responseHuman phase IDose-dependent decreasePotent anti-tumor agentAntigen-specific monoclonal antibodiesAnti-tumor agentsCancer ptsQ3 weeksResistant HER2Transaminase elevationHepatic transaminasesPartial response