2022
Safety and activity of anti-mesothelin antibody–drug conjugate anetumab ravtansine in combination with pegylated-liposomal doxorubicin in platinum-resistant ovarian cancer: multicenter, phase Ib dose escalation and expansion study
Santin A, Vergote I, González-Martín A, Moore K, Oaknin A, Romero I, Diab S, Copeland L, Monk B, Coleman R, Herzog T, Siegel J, Kasten L, Schlicker A, Schulz A, Köchert K, Walter A, Childs B, Elbi C, Bulat I. Safety and activity of anti-mesothelin antibody–drug conjugate anetumab ravtansine in combination with pegylated-liposomal doxorubicin in platinum-resistant ovarian cancer: multicenter, phase Ib dose escalation and expansion study. International Journal Of Gynecological Cancer 2022, 33: ijgc-2022-003927. PMID: 36564099, PMCID: PMC10086500, DOI: 10.1136/ijgc-2022-003927.Peer-Reviewed Original ResearchConceptsPlatinum-resistant ovarian cancerProgression-free survivalMedian progression-free survivalAnetumab ravtansineObjective response rateOvarian cancerLiposomal doxorubicinMedian durationAdverse eventsDose escalationMesothelin expressionCommon treatment-emergent adverse eventsPlatinum-resistant epithelial ovarian cancerResponse rateAnti-mesothelin monoclonal antibodyTreatment-emergent adverse eventsHigh mesothelin expressionPegylated-liposomal doxorubicinPhase Ib studyPhase III studyDose-limiting toxicityPromising clinical activityEpithelial ovarian cancerAnti-tumor activityCentral immunohistochemistry
2020
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
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 trials
2017
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
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, Pettinella F, Masserdotti A, Zammataro L, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi D, Azodi M, Schwartz P, Santin A. SYD985, a novel duocarmycin-based HER2-targeting antibody-drug conjugate, shows promising antitumor activity in epithelial ovarian carcinoma with HER2/neu expression. Journal Of Clinical Oncology 2017, 35: e14009-e14009. DOI: 10.1200/jco.2017.35.15_suppl.e14009.Peer-Reviewed Original ResearchHER2/neu expressionHER2/neu 3Epithelial ovarian cancerAntibody-dependent cellular cytotoxicityAntibody-drug conjugatesT-DM1Neu expressionEOC cell linesNeu 3Low HER2/neu expressionHER2/neu 2HER2-targeting antibody-drug conjugateHER2 overexpression/amplificationNovel antibody-drug conjugateNovel HER2-targeting antibody-drug conjugateCell linesChemo-resistant diseaseEpithelial ovarian carcinomaOvarian cancer xenograftsLethal gynecological cancerOverexpression/amplificationAnti-tumor activityMonoclonal antibody trastuzumabEffector cellsEOC patientsSYD985, 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 carcinomaSYD985