2024
Efficacy and Safety of Sacituzumab Govitecan in Patients With Advanced Solid Tumors (TROPiCS-03): Analysis in Patients With Advanced Endometrial Cancer.
Santin A, Corr B, Spira A, Willmott L, Butrynski J, Tse K, Patel J, Mekan S, Wu T, Lin K, Kuo P, Dumbrava E. Efficacy and Safety of Sacituzumab Govitecan in Patients With Advanced Solid Tumors (TROPiCS-03): Analysis in Patients With Advanced Endometrial Cancer. Journal Of Clinical Oncology 2024, jco2302767. PMID: 39083724, DOI: 10.1200/jco.23.02767.Peer-Reviewed Original ResearchProgression-free survivalDuration of responseTreatment-related adverse eventsAdvanced endometrial cancerEndometrial cancerSacituzumab govitecanTrop-2Investigator assessmentSolid tumorsTrophoblast cell surface antigen 2Median duration of responsePhase II basket studyMedian progression-free survivalEnd pointsBaseline tumor specimensClinical benefit ratePlatinum-based therapyStudy drug discontinuationAdvanced solid tumorsMedian follow-upMetastatic solid tumorsTrop-2 expressionSecondary end pointsPrimary end pointEfficacy of SG
2020
Sacituzumab govitecan (SG) in patients (pts) with previously treated metastatic endometrial cancer (mEC): results from a phase I/II study.
Santin A, Komiya T, Goldenberg D, Sharkey R, Hong Q, Wegener W, Goswami T, Bardia A. Sacituzumab govitecan (SG) in patients (pts) with previously treated metastatic endometrial cancer (mEC): results from a phase I/II study. Journal Of Clinical Oncology 2020, 38: 6081-6081. DOI: 10.1200/jco.2020.38.15_suppl.6081.Peer-Reviewed Original ResearchMetastatic endometrial cancerObjective response rateClinical benefit rateProgression-free survivalDuration of responseMedian overall survivalSacituzumab govitecanOverall survivalTrop-2 expressionPlatinum therapyPhase I/II studySolid tumorsTrop-2Median progression-free survivalNeutrophil count decreasePrevious preclinical findingsPrior platinum therapySimilar safety profileAdvanced solid tumorsCT/MRI scansMetastatic solid tumorsLimited treatment optionsFurther clinical investigationFebrile neutropeniaPrior chemotherapyTROPiCS–03: A phase II open-label study of sacituzumab govitecan (SG) in patients with metastatic solid tumors.
Saxena A, Michel L, Hong Q, Hilsinger K, Kanwal C, Pichardo C, Goswami T, Santin A. TROPiCS–03: A phase II open-label study of sacituzumab govitecan (SG) in patients with metastatic solid tumors. Journal Of Clinical Oncology 2020, 38: tps3648-tps3648. DOI: 10.1200/jco.2020.38.15_suppl.tps3648.Peer-Reviewed Original ResearchMetastatic solid tumorsSacituzumab govitecanTrop-2 expressionSolid tumorsPhase II open-label studyPrior platinum-based chemotherapyCell death protein 1Neck squamous cell carcinomaActive CNS metastasesClinical benefit rateOverall safety populationManageable safety profileObjective response rateOpen-label studyLow discontinuation ratePhase 2 studyProgression-free survivalPlatinum-based chemotherapyDeath protein 1Duration of responseSquamous cell carcinomaCell surface antigensBiomarker enrichment strategiesMultiple tumor typesTopoisomerase I inhibitorPreclinical Activity of Sacituzumab Govitecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2 (Trop-2) Linked to the Active Metabolite of Irinotecan (SN-38), in Ovarian Cancer
Perrone E, Lopez S, Zeybek B, Bellone S, Bonazzoli E, Pelligra S, Zammataro L, Manzano A, Manara P, Bianchi A, Buza N, Tymon-Rosario J, Altwerger G, Han C, Menderes G, Ratner E, Silasi DA, Azodi M, Hui P, Schwartz PE, Scambia G, Santin AD. Preclinical Activity of Sacituzumab Govitecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2 (Trop-2) Linked to the Active Metabolite of Irinotecan (SN-38), in Ovarian Cancer. Frontiers In Oncology 2020, 10: 118. PMID: 32117765, PMCID: PMC7028697, DOI: 10.3389/fonc.2020.00118.Peer-Reviewed Original ResearchTrop-2 expressionEOC cell linesSacituzumab govitecanEpithelial ovarian cancerPrimary tumor cell linesPreclinical activityTrop-2EOC xenograftsOvarian cancerTrophoblast cell surface antigen 2Cell linesActive metaboliteTumor cell linesImpressive anti-tumor activityCell surface antigen 2Lethal gynecologic malignancyHigh ADCC activityAnti-tumor activityParaffin-embedded tumorsSignificant bystander killingGynecologic malignanciesADCC activityEOC tissuesOvarian tumorsClinical trialsPreclinical activity of sacituzumab govitecan (IMMU-132) in uterine and ovarian carcinosarcomas
Lopez S, Perrone E, Bellone S, Bonazzoli E, Zeybek B, Han C, Tymon-Rosario J, Altwerger G, Menderes G, Bianchi A, Zammataro L, Manzano A, Manara P, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Raspagliesi F, Angioli R, Buza N, Hui P, Bond HM, Santin AD. Preclinical activity of sacituzumab govitecan (IMMU-132) in uterine and ovarian carcinosarcomas. Oncotarget 2020, 11: 560-570. PMID: 32082489, PMCID: PMC7007291, DOI: 10.18632/oncotarget.27342.Peer-Reviewed Original ResearchSacituzumab govitecanTrop-2 expressionTrop-2Ovarian carcinosarcomaWeekly intravenous administrationSignificant tumor growth inhibitionTumor growth inhibitionCS cell linesCell linesCell surface markersNegative cell linesAggressive carcinosarcomasCarcinosarcoma patientsPrimary carcinosarcomaOverall survivalPoor prognosisPreclinical activityRare cancersIntravenous administrationXenograft modelActive drugCarcinosarcomaActive metaboliteFFPE tumorsCell viability assaysCervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan
Zeybek B, Manzano A, Bianchi A, Bonazzoli E, Bellone S, Buza N, Hui P, Lopez S, Perrone E, Manara P, Zammataro L, Altwerger G, Han C, Tymon-Rosario J, Menderes G, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin A. Cervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan. Scientific Reports 2020, 10: 973. PMID: 31969666, PMCID: PMC6976591, DOI: 10.1038/s41598-020-58009-3.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaSacituzumab govitecanTrop-2 expressionAntibody-drug conjugatesCell surface markersXenograft modelTrop-2Adenocarcinoma/adenosquamous carcinomaAnti-Trop-2 antibodyCell linesWeekly intravenous administrationSignificant tumor growth inhibitionCervical cancer patientsPrimary cervical cancerStrong diffuse stainingPrimary cervical tumorsCervical cancer cell linesEpithelial solid tumorsReal-time polymerase chain reactionTumor growth inhibitionHuman placental tissuePositive cell linesNegative cell linesVivo antitumor activityCancer cell linesSacituzumab govitecan, an antibody‐drug conjugate targeting trophoblast cell‐surface antigen 2, shows cytotoxic activity against poorly differentiated endometrial adenocarcinomas in vitro and in vivo
Perrone E, Manara P, Lopez S, Bellone S, Bonazzoli E, Manzano A, Zammataro L, Bianchi A, Zeybek B, Buza N, Tymon‐Rosario J, Altwerger G, Han C, Menderes G, Huang GS, Ratner E, Silasi D, Azodi M, Hui P, Schwartz PE, Scambia G, Santin AD. Sacituzumab govitecan, an antibody‐drug conjugate targeting trophoblast cell‐surface antigen 2, shows cytotoxic activity against poorly differentiated endometrial adenocarcinomas in vitro and in vivo. Molecular Oncology 2020, 14: 645-656. PMID: 31891442, PMCID: PMC7053235, DOI: 10.1002/1878-0261.12627.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmAntineoplastic AgentsCamptothecinCarcinoma, EndometrioidCell Adhesion MoleculesCell DifferentiationCell Line, TumorCell SurvivalEndometrial NeoplasmsFemaleHumansImmunoconjugatesImmunohistochemistryIrinotecanMiceMice, SCIDTissue Array AnalysisXenograft Model Antitumor AssaysConceptsAntibody-dependent cell cytotoxicityCell surface antigen 2EC cell linesSacituzumab govitecanTrop-2 expressionPrimary tumor cell linesTrop-2Xenograft modelAntigen 2Cell linesTumor cell linesCommon gynecologic malignancyFuture clinical trialsChromium release assaysParaffin-embedded tumorsTumor growth inhibitionSignificant bystander killingEC xenograftsGynecologic malignanciesEndometrial cancerEndometrial adenocarcinomaEndometrioid carcinoma tissuesPreclinical activityControl antibodyClinical trials
2019
In vitro and in vivo activity of sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (Trop-2) in uterine serous carcinoma
Han C, Perrone E, Zeybek B, Bellone S, Tymon-Rosario J, Altwerger G, Menderes G, Feinberg J, Haines K, Muller Karger ME, Bianchi A, Zammataro L, Manzano A, Bonazzoli E, Manara P, Buza N, Hui P, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Lopez S, Santin AD. In vitro and in vivo activity of sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (Trop-2) in uterine serous carcinoma. Gynecologic Oncology 2019, 156: 430-438. PMID: 31839338, DOI: 10.1016/j.ygyno.2019.11.018.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmCamptothecinCell Adhesion MoleculesCell Line, TumorCystadenocarcinoma, SerousFemaleFlow CytometryHumansImmunoconjugatesImmunohistochemistryMiceMice, SCIDMolecular Targeted TherapyRandom AllocationTissue Array AnalysisUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaCell surface antigen 2Sacituzumab govitecanTrop-2 expressionTrop-2Serous carcinomaAntigen 2Advanced/recurrent diseasePrimary uterine serous carcinomaResistant human tumorsSignificant bystander killingUSC patientsUSC xenograftsRecurrent diseaseClinical responseEndometrial cancerAggressive variantPoor prognosisPreclinical activityPrimary tumorIntravenous administrationClinical developmentUSC samplesActive metaboliteSN-3893 Sacituzumab govitecan in uterine and ovarian carcinosarcomas
Lopez S, Perrone E, Zeybek B, Bellone S, Manzano A, Zammataro L, Han C, Altwerger G, Angioli R, Santin A. 93 Sacituzumab govitecan in uterine and ovarian carcinosarcomas. International Journal Of Gynecological Cancer 2019, 29: a48. DOI: 10.1136/ijgc-2019-igcs.93.Peer-Reviewed Original ResearchCS cell linesAntibody-drug conjugatesSacituzumab govitecanTrop-2 expressionTrop-2Negative tumorsCell linesControl antibody drug conjugatesNovel antibody-drug conjugateAggressive gynecologic malignancyGreater antitumor effectPrimary tumor cell linesRemarkable antitumor activityAggressive carcinosarcomasGynecologic malignanciesOvarian carcinosarcomaPrimary tumorClinical trialsEpithelial tumorsSarcomatous elementsAntitumor effectsAntigen 2CarcinosarcomaActive metaboliteSN-3851 In vitro and in vivo activity of sacituzumab govitecan, in ovarian cancer
Perrone E, Lopez S, Zeibek B, Bellone S, Zammataro L, Manzano A, Bonazzoli E, Manara P, Scambia G, Santin A. 51 In vitro and in vivo activity of sacituzumab govitecan, in ovarian cancer. International Journal Of Gynecological Cancer 2019, 29: a29. DOI: 10.1136/ijgc-2019-igcs.51.Peer-Reviewed Original ResearchEpithelial ovarian cancerTrop-2 expressionSacituzumab govitecanPrimary tumor cell linesEOC cell linesTrop-2EOC xenograftsOvarian cancerCell linesTumor cell linesAggressive epithelial ovarian cancerLethal gynecologic malignancyHigh ADCC activityGreater antitumor effectParaffin-embedded tumorsGynecologic malignanciesADCC activityOvarian tumorsPreclinical activityClinical trialsEpithelial tumorsSignificant bystander effectAntitumor effectsStrong stainingActive metaboliteCervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan.
Zeybek B, Manzano A, Bianchi A, Bonazzoli E, Buza N, Lopez S, Perrone E, Manara P, Bellone S, Zammataro L, Santin A. Cervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan. Journal Of Clinical Oncology 2019, 37: e17028-e17028. DOI: 10.1200/jco.2019.37.15_suppl.e17028.Peer-Reviewed Original ResearchSquamous cell carcinomaPrimary cervical cancer cell linesControl antibody drug conjugatesAntibody-drug conjugatesIMMU-132Clear cell carcinomaTrop-2 expressionCervical cancer cell linesCell carcinomaCancer cell linesCervical cancerSacituzumab govitecanNeuroendocrine carcinomaCervical tumorsCell linesTrop-2Cervical cancer cell viabilityNaked antibodiesWeekly intravenous administrationSignificant tumor growth inhibitionStrong diffuse stainingUnmet medical needPrimary tumor cell linesReal-time polymerase chain reactionTumor growth inhibition
2011
Trop-2 Overexpression in Poorly Differentiated Endometrial Endometrioid Carcinoma
Bignotti E, Ravaggi A, Romani C, Falchetti M, Lonardi S, Facchetti F, Pecorelli S, Varughese J, Cocco E, Bellone S, Schwartz PE, Rutherford TJ, Santin AD. Trop-2 Overexpression in Poorly Differentiated Endometrial Endometrioid Carcinoma. International Journal Of Gynecological Cancer 2011, 21: 1613-1621. PMID: 21892093, PMCID: PMC3233648, DOI: 10.1097/igc.0b013e318228f6da.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmCarcinoma, EndometrioidCell Adhesion MoleculesCell DifferentiationCell Line, TumorComplement System ProteinsEndometrial NeoplasmsFemaleFlow CytometryHumansImmunization, PassiveImmunoglobulin GImmunohistochemistryRNA, MessengerConceptsEndometrial endometrioid carcinomaNormal endometrial controlsTrop-2 expressionEEC cell linesAntibody-dependent cellular cytotoxicityReal-time polymerase chain reactionQuantitative real-time polymerase chain reactionEndometrioid carcinomaPolymerase chain reactionCellular cytotoxicityTrop-2Anti-Trop-2 antibodyCell linesTherapeutic agentsCr-release assaysTrop-2 overexpressionGrade 3 tumorsStandard treatment modalityChain reactionNovel therapeutic agentsCell surface markersEndometrial controlTreatment modalitiesPrimary cell linesEEC samplesCervical carcinomas overexpress human trophoblast cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized monoclonal anti-Trop-2 antibody
Varughese J, Cocco E, Bellone S, Ratner E, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Buza N, Pecorelli S, Santin AD. Cervical carcinomas overexpress human trophoblast cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized monoclonal anti-Trop-2 antibody. American Journal Of Obstetrics And Gynecology 2011, 205: 567.e1-567.e7. PMID: 21889762, PMCID: PMC3224189, DOI: 10.1016/j.ajog.2011.06.093.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAntibodies, MonoclonalAntigens, NeoplasmBiomarkers, TumorCarcinoma, Squamous CellCell Adhesion MoleculesCell Line, TumorComplement System ProteinsDrug Resistance, NeoplasmDrug SynergismFemaleFlow CytometryGene Expression Regulation, NeoplasticHumansImmunoglobulin GInterleukin-2Killer Cells, NaturalReal-Time Polymerase Chain ReactionUterine Cervical NeoplasmsConceptsAntibody-dependent cell-mediated cytotoxicityAnti-Trop-2 antibodyTrop-2 expressionReal-time polymerase chain reactionCell surface markersCervical cancerPolymerase chain reactionHighest messenger RNA expressionCell-dependent cytotoxicityCell-mediated cytotoxicityNovel treatment optionsChromium release assaysConventional treatment modalitiesChain reactionComplement-dependent cytotoxicityEffects of interleukinMessenger RNA expressionLevel of cytotoxicityCancer refractoryCervical carcinomaTreatment optionsTreatment modalitiesIL-2Normal cervixRelease assaysHigh-grade, chemotherapy-resistant primary ovarian carcinoma cell lines overexpress human trophoblast cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized monoclonal anti-Trop-2 antibody
Varughese J, Cocco E, Bellone S, Bellone M, Todeschini P, Carrara L, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. High-grade, chemotherapy-resistant primary ovarian carcinoma cell lines overexpress human trophoblast cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized monoclonal anti-Trop-2 antibody. Gynecologic Oncology 2011, 122: 171-177. PMID: 21453957, PMCID: PMC3104081, DOI: 10.1016/j.ygyno.2011.03.002.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibody-Dependent Cell CytotoxicityAntigens, NeoplasmCell Adhesion MoleculesCell Line, TumorDrug Resistance, NeoplasmFemaleFlow CytometryHumansImmunoglobulin GImmunohistochemistryInterleukin-2Killer Cells, NaturalMiddle AgedMolecular Targeted TherapyOvarian NeoplasmsRNA, MessengerConceptsAntibody-dependent cellular cytotoxicityOvarian cancer cell linesTrop-2 expressionAnti-Trop-2 antibodyChemotherapy-resistant ovarian cancerPrimary ovarian cancer cell linesCancer cell linesOvarian carcinoma cell linesInterleukin-2Cell surface markersCarcinoma cell linesOvarian cancerCell linesTrop-2Therapeutic agentsChemotherapy-resistant diseaseNovel therapeutic agentsEffect of serumOvarian diseaseControl antibodyHRS7Real-time PCRCellular cytotoxicityCarcinoma specimensRelease assaysUterine serous papillary carcinomas overexpress human trophoblast‐cell‐surface marker (trop‐2) and are highly sensitive to immunotherapy with hRS7, a humanized anti‐trop‐2 monoclonal antibody
Varughese J, Cocco E, Bellone S, de Leon M, Bellone M, Todeschini P, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Uterine serous papillary carcinomas overexpress human trophoblast‐cell‐surface marker (trop‐2) and are highly sensitive to immunotherapy with hRS7, a humanized anti‐trop‐2 monoclonal antibody. Cancer 2011, 117: 3163-3172. PMID: 21246534, PMCID: PMC3128671, DOI: 10.1002/cncr.25891.Peer-Reviewed Original ResearchConceptsUterine serous papillary carcinomaPrimary USPC cell linesUSPC cell linesAntibody-dependent cellular cytotoxicitySerous papillary carcinomaTrop-2 expressionReal-time polymerase chain reactionPolymerase chain reactionTrop-2Papillary carcinomaCell linesMonoclonal antibodiesChemotherapy-resistant variantsNatural killer cytotoxicityStandard treatment modalityUterine serous carcinomaComplement-dependent cytotoxicityNovel therapeutic strategiesNovel therapeutic agentsKiller cytotoxicityEndometrial cancerSerous carcinomaTreatment modalitiesControl antibodyHRS7
2010
Trop-2 overexpression as an independent marker for poor overall survival in ovarian carcinoma patients
Bignotti E, Todeschini P, Calza S, Falchetti M, Ravanini M, Tassi RA, Ravaggi A, Bandiera E, Romani C, Zanotti L, Tognon G, Odicino FE, Facchetti F, Pecorelli S, Santin AD. Trop-2 overexpression as an independent marker for poor overall survival in ovarian carcinoma patients. European Journal Of Cancer 2010, 46: 944-953. PMID: 20060709, DOI: 10.1016/j.ejca.2009.12.019.Peer-Reviewed Original ResearchConceptsEpithelial ovarian cancerTrop-2 overexpressionTrop-2 expressionOverall survivalPrognostic factorsProtein overexpressionTrop-2 protein expressionMultivariate Cox regression analysisConventional clinicopathological featuresPresence of ascitesCox regression analysisLymph node metastasisOvarian carcinoma patientsPoor overall survivalIndependent prognostic markerNovel prognostic factorUnivariate survival analysisAggressive malignant phenotypeImmunotherapeutic strategiesShort-term cultureCarcinoma patientsClinical courseNode metastasisClinicopathological featuresPrognostic significance