2020
First-in-Human, Multicenter, Phase I Dose-Escalation and Expansion Study of Anti-Mesothelin Antibody–Drug Conjugate Anetumab Ravtansine in Advanced or Metastatic Solid Tumors
Hassan R, Blumenschein GR, Moore KN, Santin AD, Kindler HL, Nemunaitis JJ, Seward SM, Thomas A, Kim SK, Rajagopalan P, Walter AO, Laurent D, Childs BH, Sarapa N, Elbi C, Bendell JC. First-in-Human, Multicenter, Phase I Dose-Escalation and Expansion Study of Anti-Mesothelin Antibody–Drug Conjugate Anetumab Ravtansine in Advanced or Metastatic Solid Tumors. Journal Of Clinical Oncology 2020, 38: 1824-1835. PMID: 32213105, PMCID: PMC7255978, DOI: 10.1200/jco.19.02085.Peer-Reviewed Original ResearchConceptsAnetumab ravtansineDose-escalation cohortsMetastatic solid tumorsAnti-mesothelin antibodySolid tumorsExpansion cohortClinical activityCommon drug-related adverse eventsDrug-related adverse eventsPhase I Dose-EscalationMultiple solid tumor typesPhase IDose-expansion studyI Dose-EscalationPeripheral sensory neuropathyPhase II studyRecurrent ovarian cancerRecurrent solid tumorsPreliminary antitumor activityDrug-related deathsFavorable pharmacokinetic profileSolid tumor typesAntibody-drug conjugatesStable diseaseAdult patients
2018
In vitro and in vivo activity of IMGN853, an Antibody-Drug Conjugate targeting Folate Receptor Alpha linked to DM4, in biologically aggressive endometrial cancers
Altwerger G, Bonazzoli E, Bellone S, Egawa-Takata T, Menderes G, Pettinella F, Bianchi A, Riccio F, Feinberg J, Zammataro L, Han C, Yadav G, Dugan K, Morneault A, Ponte JF, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin AD. In vitro and in vivo activity of IMGN853, an Antibody-Drug Conjugate targeting Folate Receptor Alpha linked to DM4, in biologically aggressive endometrial cancers. Molecular Cancer Therapeutics 2018, 17: molcanther.0930.2017. PMID: 29440294, PMCID: PMC5932245, DOI: 10.1158/1535-7163.mct-17-0930.Peer-Reviewed Original ResearchConceptsEndometrial cancerXenograft modelCell linesTumor cell linesPatient-derived xenograft modelsUterine cancer cell linesAggressive endometrial cancersEndometrial cancer deathsExpression of FRαPrimary USC cell linesRecurrent endometrial cancerReceptor alpha expressionUSC cell linesImpressive antitumor activityMol Cancer TherUSC patientsCancer cell linesMedian survivalCancer deathPDX modelsPreclinical dataUterine cancerComplete resolutionIMGN853Grade 3
2017
SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody–Drug Conjugate, Shows Antitumor Activity in Uterine and Ovarian Carcinosarcoma with HER2/Neu Expression
Menderes G, Bonazzoli E, Bellone S, Black J, Predolini F, Pettinella F, Masserdotti A, Zammataro L, Altwerger G, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi DA, Azodi M, Schwartz PE, Santin AD. SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody–Drug Conjugate, Shows Antitumor Activity in Uterine and Ovarian Carcinosarcoma with HER2/Neu Expression. Clinical Cancer Research 2017, 23: 5836-5845. PMID: 28679774, PMCID: PMC5626613, DOI: 10.1158/1078-0432.ccr-16-2862.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAnimalsAntibody-Dependent Cell CytotoxicityCarcinosarcomaCell Line, TumorCell ProliferationDuocarmycinsFemaleGene Expression Regulation, NeoplasticHumansImmunoconjugatesIndolesMaytansineMiceOvarian NeoplasmsPyrrolidinonesReceptor, ErbB-2TrastuzumabUterine NeoplasmsXenograft Model Antitumor AssaysConceptsAntibody-dependent cellular cytotoxicityHER2/neu expressionHER2/neu 3T-DM1Antibody-drug conjugatesCS cell linesNeu expressionEffector cellsHigh HER2/neu expressionNeu 3HER2-targeting antibody-drug conjugateCell linesBystander killingPatient-derived xenograft modelsNovel HER2-targeting antibody-drug conjugateAggressive gynecologic malignancyHigh HER2 expressionEffective antibody-drug conjugatesHER2/neuClin Cancer ResGynecologic malignanciesOvarian carcinosarcomaHER2 expressionTrastuzumab emtansineSYD985Superior in vitro and in vivo activity of trastuzumab-emtansine (T-DM1) in comparison to trastuzumab, pertuzumab and their combination in epithelial ovarian carcinoma with high HER2/neu expression
Menderes G, Bonazzoli E, Bellone S, Altwerger G, Black JD, Dugan K, Pettinella F, Masserdotti A, Riccio F, Bianchi A, Zammataro L, de Haydu C, Buza N, Hui P, Wong S, Huang GS, Litkouhi B, Ratner E, Silasi DA, Azodi M, Schwartz PE, Santin AD. Superior in vitro and in vivo activity of trastuzumab-emtansine (T-DM1) in comparison to trastuzumab, pertuzumab and their combination in epithelial ovarian carcinoma with high HER2/neu expression. Gynecologic Oncology 2017, 147: 145-152. PMID: 28705408, PMCID: PMC5605415, DOI: 10.1016/j.ygyno.2017.07.009.Peer-Reviewed Original ResearchConceptsHigh HER2/neu expressionHER2/neu expressionEpithelial ovarian cancerHER2/neuAnti-tumor activityEOC cell linesT-DM1Neu expressionChemotherapy-resistant epithelial ovarian cancerLimited anti-tumor activityAntibody-dependent cell-mediated cytotoxicity (ADCC) activityCell linesSuperior anti-tumor activityCombination of trastuzumabLethal gynecologic malignancyEpithelial ovarian carcinomaTumor growth inhibitionEOC xenograftsGynecologic malignanciesPreclinical dataOvarian carcinomaOvarian cancerClinical studiesXenograft modelSingle agentSYD985, a novel duocarmycin-based HER2-targeting antibody-drug conjugate, shows promising antitumor activity in epithelial ovarian carcinoma with HER2/Neu expression
Menderes G, Bonazzoli E, Bellone S, Black J, Altwerger G, Masserdotti A, Pettinella F, Zammataro L, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin AD. SYD985, a novel duocarmycin-based HER2-targeting antibody-drug conjugate, shows promising antitumor activity in epithelial ovarian carcinoma with HER2/Neu expression. Gynecologic Oncology 2017, 146: 179-186. PMID: 28473206, PMCID: PMC5533304, DOI: 10.1016/j.ygyno.2017.04.023.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAgedAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntineoplastic Agents, AlkylatingBystander EffectCarcinoma, Ovarian EpithelialCell Line, TumorDuocarmycinsFemaleHumansImmunotoxinsIndolesMaytansineMiceMice, SCIDMiddle AgedNeoplasms, Glandular and EpithelialOvarian NeoplasmsPyrrolidinonesRandom AllocationReceptor, ErbB-2TrastuzumabXenograft Model Antitumor AssaysConceptsHER2/neu expressionAntibody-dependent cellular cytotoxicityEpithelial ovarian cancerLow HER2/neu expressionPeripheral blood lymphocytesHER2/neu 3Antibody-drug conjugatesT-DM1Neu expressionEOC cell linesNeu 3HER2-targeting antibody-drug conjugateNovel antibody-drug conjugateNovel HER2-targeting antibody-drug conjugateEpithelial ovarian carcinomaOvarian cancer xenograftsAnti-tumor activityCell linesEOC xenograftsTrastuzumab emtansineCancer xenograftsBlood lymphocytesOvarian cancerOvarian carcinomaSYD985Objective, domain-specific HER2 measurement in uterine and ovarian serous carcinomas and its clinical significance
Carvajal-Hausdorf DE, Schalper KA, Bai Y, Black J, Santin AD, Rimm DL. Objective, domain-specific HER2 measurement in uterine and ovarian serous carcinomas and its clinical significance. Gynecologic Oncology 2017, 145: 154-158. PMID: 28196634, PMCID: PMC5941302, DOI: 10.1016/j.ygyno.2017.02.002.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAfatinibAntibodies, Monoclonal, HumanizedAntineoplastic AgentsCohort StudiesExtracellular SpaceFemaleFluorescent Antibody TechniqueHumansIntracellular SpaceLapatinibMaytansineMiddle AgedNeoplasms, Cystic, Mucinous, and SerousOvarian NeoplasmsProtein DomainsQuinazolinesReceptor, ErbB-2Retrospective StudiesTissue Array AnalysisTrastuzumabUterine NeoplasmsConceptsUterine serous carcinomaOvarian serous carcinomaHER2 intracellular domainSerous carcinomaECD levelsECD statusTissue microarrayHER2 measurementQuantitative immunofluorescenceHER2 overexpression/amplificationClinico-pathologic characteristicsClinico-pathological featuresHER2-targeted agentsIntracellular domainOverexpression/amplificationHER2 extracellular domainExtracellular domainOSC patientsClinical trialsBreast cancerClinical significancePatientsHER2 assaysP95-HER2Carcinoma
2014
T-DM1, a novel antibody-drug conjugate, is highly effective against uterine and ovarian carcinosarcomas overexpressing HER2
Nicoletti R, Lopez S, Bellone S, Cocco E, Schwab CL, Black JD, Centritto F, Zhu L, Bonazzoli E, Buza N, Hui P, Mezzanzanica D, Canevari S, Schwartz PE, Rutherford TJ, Santin AD. T-DM1, a novel antibody-drug conjugate, is highly effective against uterine and ovarian carcinosarcomas overexpressing HER2. Clinical & Experimental Metastasis 2014, 32: 29-38. PMID: 25398397, PMCID: PMC4310789, DOI: 10.1007/s10585-014-9688-8.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntineoplastic AgentsCarcinosarcomaCell Line, TumorCell ProliferationFemaleImmunoconjugatesM Phase Cell Cycle CheckpointsMaytansineMiceMice, SCIDOvarian NeoplasmsReceptor, ErbB-2TrastuzumabUterine NeoplasmsXenograft Model Antitumor AssaysConceptsCS cell linesT-DM1Cell linesFlow cytometryNovel antibody-drug conjugateAggressive clinical behaviorNovel treatment optionsG2/M phase cell cycle arrestHER2 protein overexpressionM phase cell cycle arrestPhase cell cycle arrestAntibody-drug conjugatesDisease refractoryPrimary HER2Vehicle miceOvarian carcinosarcomaPoor prognosisUterine carcinosarcomaCS patientsTreatment optionsClinical behaviorLonger survivalCell cycle arrestHER2 amplificationCarcinosarcomaT‐DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo
English DP, Bellone S, Schwab CL, Bortolomai I, Bonazzoli E, Cocco E, Buza N, Hui P, Lopez S, Ratner E, Silasi D, Azodi M, Schwartz PE, Rutherford TJ, Santin AD. T‐DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo. Cancer Medicine 2014, 3: 1256-1265. PMID: 24890382, PMCID: PMC4302675, DOI: 10.1002/cam4.274.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAgedAged, 80 and overAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntineoplastic AgentsApoptosisCarcinomaCell Cycle CheckpointsCell ProliferationDisease Models, AnimalFemaleGene AmplificationGene ExpressionGene Expression Regulation, NeoplasticHumansImmunohistochemistryIn Situ Hybridization, FluorescenceMaytansineMiddle AgedReceptor, ErbB-2RNA, MessengerTrastuzumabUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaUSC cell linesNovel antibody-drug conjugateT-DM1USC xenograftsAntibody-drug conjugatesSerous carcinomaAntibody-dependent cell-mediated cytotoxicityEpidermal growth factor receptor 2Cell linesPrimary USC cell linesGrowth factor receptor 2Cell-mediated cytotoxicityChromium release assaysNovel treatment optionsHER2 protein overexpressionFactor receptor 2HER2 gene amplificationHER2 protein expressionC-erbB2 gene amplificationGene amplificationDisease refractoryPrimary HER2USC cellsUSC patients