2024
Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147)
Sheth S, Oh J, Bellone S, Siegel E, Greenman M, Mutlu L, McNamara B, Pathy S, Clark M, Azodi M, Altwerger G, Andikyan V, Huang G, Ratner E, Kim D, Iwasaki A, Levi A, Buza N, Hui P, Flaherty S, Schwartz P, Santin A. Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147). Clinical Cancer Research 2024, 30: of1-of10. PMID: 38592381, DOI: 10.1158/1078-0432.ccr-23-3639.Peer-Reviewed Original ResearchConceptsRandomized phase II trialCD4/CD8 T cellsT cellsHPV clearanceArm BNo significant differenceClinical surveillanceRate of HPV clearanceSecondary outcomesPre-neoplastic cervical lesionsCervical intraepithelial neoplasiaT cell infiltrationT cell responsesSignificant differenceCIN3 patientsIntraepithelial neoplasiaArm ACervical lesionsImiquimod groupSurveillance armVaginal suppositoriesProspective trialsArm CHPV vaccinationImiquimodRandomized phase II trial of weekly ixabepilone with or without biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer: Updated survival and subgroup analyses
Roque D, Siegel E, Buza N, Bellone S, Huang G, Andikyan V, Clark M, Azodi M, Schwartz P, Rao G, Xu F, Hui P, Altwerger G, Ratner E, Santin A. Randomized phase II trial of weekly ixabepilone with or without biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer: Updated survival and subgroup analyses. Gynecologic Oncology 2024, 190: s299-s301. DOI: 10.1016/j.ygyno.2024.07.449.Peer-Reviewed Original ResearchUtility of next generation sequencing to unequivocally establish clonality in synchronous vs metastatic endometrial and ovarian carcinomas
Greenman M, Bellone S, Hartwich T, Buza N, Santin A. Utility of next generation sequencing to unequivocally establish clonality in synchronous vs metastatic endometrial and ovarian carcinomas. Gynecologic Oncology Reports 2024, 56: 101524. PMID: 39435258, PMCID: PMC11492078, DOI: 10.1016/j.gore.2024.101524.Peer-Reviewed Original ResearchOvarian carcinomaNext generation sequencingPrimary uterine tumorsDiagnostically challenging casesOvarian tumorsPrimary tumorUterine tumorsEndometrial malignancyMetastatic tumorsAdjuvant treatmentClonal relationshipTargeted therapyUtilization of next generation sequencingTumor clonalityGeneration sequencingProtein expression profilesTumorChallenging casesImprove outcomesCarcinomaGold standardGenetic landscapeMalignancyClonalityExpression profilesTrastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2
Mutlu L, McNamara B, Bellone S, Manavella D, Demirkiran C, Greenman M, Verzosa M, Buza N, Hui P, Hartwich T, Harold J, Yang-Hartwich Y, Zipponi M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Santin A. Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2. Clinical & Experimental Metastasis 2024, 41: 765-775. PMID: 38909139, DOI: 10.1007/s10585-024-10297-z.Peer-Reviewed Original ResearchHigh-grade serous ovarian cancerClear cell carcinomaHER2-targeting antibody-drug conjugateAntibody-drug conjugatesT-DXdReceptor over-expressionTrastuzumab deruxtecanXenograft modelCell linesOvarian clear cell carcinomaOvarian cancer cell linesTumors overexpressing HER2Biologically aggressive tumorsFluorescence in situ hybridization assaySerous ovarian cancerEffective antibody-drug conjugatesIn vivo antitumor activityMouse xenograft modelMetastatic cell linesDS-8201aCancer cell linesAggressive tumorsHER2 expressionCell carcinomaOvarian cancerRandomized phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer (NCT03093155): Updated survival and subgroup analyses
Roque D, Siegel E, Buza N, Bellone S, Huang G, Altwerger G, Andikyan V, Clark M, Azodi M, Schwartz P, Rao G, Ratner E, Santin A. Randomized phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer (NCT03093155): Updated survival and subgroup analyses. BJC Reports 2024, 2: 43. PMID: 39516558, PMCID: PMC11523995, DOI: 10.1038/s44276-024-00067-5.Peer-Reviewed Original ResearchPre-treated ovarian cancerOverall survivalBev armsDose reductionOvarian cancerTaxane responseRandomized phase 2 trialRandomized phase II trialPaclitaxel-resistant diseaseResultsThirty-seven patientsTreated with paclitaxelPhase 2 trialBiweekly bevacizumabDays 1,8,15Taxane-sensitiveUpdate survivalProgression-freePeritoneal cancerDose modificationTaxane sensitivityPlatinum resistanceSubset analysisSubgroup analysisResponse ratePatientsCorrection: Randomised phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer
Roque D, Siegel E, Buza N, Bellone S, Silasi D, Huang G, Andikyan V, Clark M, Azodi M, Schwartz P, Rao G, Reader J, Hui P, Tymon-Rosario J, Harold J, Mauricio D, Zeybek B, Menderes G, Altwerger G, Ratner E, Santin A. Correction: Randomised phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer. British Journal Of Cancer 2024, 130: 1073-1073. PMID: 38438590, PMCID: PMC10951353, DOI: 10.1038/s41416-024-02628-4.Peer-Reviewed Original Research
2023
In Vivo and In Vitro Efficacy of Trastuzumab Deruxtecan in Uterine Serous Carcinoma.
Mutlu L, Manavella D, Bellone S, McNamara B, Harold J, Mauricio D, Siegel E, Buza N, Hui P, Hartwich T, Yang-Hartwich Y, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Dottino P, Schwartz P, Santin A. In Vivo and In Vitro Efficacy of Trastuzumab Deruxtecan in Uterine Serous Carcinoma. Molecular Cancer Therapeutics 2023, 22: 1404-1412. PMID: 37676984, DOI: 10.1158/1535-7163.mct-23-0126.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaAntibody-dependent cellular cytotoxicityT-DXdUSC patientsUSC cell linesTrastuzumab deruxtecanSerous carcinomaHER2 expressionClinical trialsRecurrent uterine serous carcinomaTopoisomerase I inhibitor payloadSignificant antibody-dependent cellular cytotoxicityCell linesMultiple tumor indicationsPrimary USC cell linesLow HER2 expressionFuture clinical trialsHigh recurrence ratePeripheral blood lymphocytesERBB2 gene amplificationGrowth suppressionHER2-overexpressing cell linesTumor growth suppressionOverall survivalStandard chemotherapyUterine Leiomyosarcomas harboring MAP2K4 gene amplification are markedly sensitive in vivo to PLX8725, a Novel MAP2K4 Inhibitor (1315)
McNamara B, Harold J, Manavella D, Bellone S, Mutlu L, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Schlessinger J, Santin A. Uterine Leiomyosarcomas harboring MAP2K4 gene amplification are markedly sensitive in vivo to PLX8725, a Novel MAP2K4 Inhibitor (1315). Gynecologic Oncology 2023, 176: s193. DOI: 10.1016/j.ygyno.2023.06.218.Peer-Reviewed Original ResearchCorrigendum to “Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma”
Harold J, Bellone S, Manavell D, Mutlu L, McNamara B, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Santin A. Corrigendum to “Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma”. Gynecologic Oncology 2023, 170: 334. PMID: 36906375, PMCID: PMC10266020, DOI: 10.1016/j.ygyno.2023.01.029.Peer-Reviewed Original ResearchTrastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate with topoisomerase I inhibitor payload, shows antitumor activity in uterine and ovarian carcinosarcoma with HER2/neu expression
Mauricio D, Bellone S, Mutlu L, McNamara B, Manavella D, Demirkiran C, Verzosa M, Buza N, Hui P, Hartwich T, Harold J, Yang-Hartwich Y, Zipponi M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Santin A. Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate with topoisomerase I inhibitor payload, shows antitumor activity in uterine and ovarian carcinosarcoma with HER2/neu expression. Gynecologic Oncology 2023, 170: 38-45. PMID: 36610380, PMCID: PMC10445234, DOI: 10.1016/j.ygyno.2022.12.018.Peer-Reviewed Original ResearchConceptsHER2/neu expressionDS-8201aAntibody-drug conjugatesNeu expressionCS cell linesTrastuzumab deruxtecanOvarian carcinosarcomaTopoisomerase I inhibitor payloadCell linesAggressive gynecologic malignancyLimited therapeutic optionsEffective antibody-drug conjugatesCarcinosarcoma cell lineGynecologic malignanciesTherapeutic optionsIsotype controlSarcomatous elementsXenograft modelBystander killingFlow cytometryTumor cellsCarcinosarcomaAntitumor activityVivo studiesVivo activity
2022
Ovarian and uterine carcinosarcomas are sensitive in vitro and in vivo to elimusertib, a novel ataxia-telangiectasia and Rad3-related (ATR) kinase inhibitor
Manavella D, McNamara B, Harold J, Bellone S, Hartwich T, Yang-Hartwich Y, Mutlu L, Zipponi M, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Dottino P, Choi J, Alexandrov L, Buza N, Hui P, Santin A. Ovarian and uterine carcinosarcomas are sensitive in vitro and in vivo to elimusertib, a novel ataxia-telangiectasia and Rad3-related (ATR) kinase inhibitor. Gynecologic Oncology 2022, 169: 98-105. PMID: 36525930, PMCID: PMC9925406, DOI: 10.1016/j.ygyno.2022.12.003.Peer-Reviewed Original ResearchConceptsHomologous recombination deficiencyCS cell linesCell linesWestern blotKinase inhibitorsOverall animal survivalProtein expressionDose-dependent increaseDose-dependent inhibitionCarcinosarcoma cell lineTumor growth inhibitionCaspase-3 expressionEndometrioid histologyAggressive malignancyUterine carcinosarcomaCS patientsPreclinical activityClinical trialsEpithelial componentAnimal survivalXenograftsApoptosis markersRecombination deficiencyP-ATRP-Chk1Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma
Harold J, Bellone S, Manavella D, Mutlu L, McNamara B, Hartwich T, Zipponi M, Yang-Hartwich Y, Demirkiran C, Verzosa M, Choi J, Dong W, Buza N, Hui P, Altwerger G, Huang G, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz P, Santin A. Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma. Gynecologic Oncology 2022, 168: 157-165. PMID: 36442427, PMCID: PMC9797429, DOI: 10.1016/j.ygyno.2022.11.014.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsUterine leiomyosarcomaVivo activityVehicle control treatmentMedian overall survivalTumor volume differencesOral scheduleWestern blot analysisOverall survivalOral gavageAggressive malignancyPDX modelsClinical trialsSCID miceTumor measurementsULMS patientsSignificant growth inhibitionNovel ATR inhibitorTumor samplesSignificant toxicityWestern blotKinase inhibitorsATRX mutationsGene mutationsControl vehicle
2021
A phase II evaluation of pembrolizumab in recurrent microsatellite instability-high (MSI-H) endometrial cancer patients with Lynch-like versus MLH-1 methylated characteristics (NCT02899793).
Roque D, Bellone S, Siegel E, Buza N, Bonazzoli E, Guglielmi A, Zammataro L, Nagarkatti N, Zaidi S, Lee J, Schwartz P, Ratner E, Alexandrov L, Iwasaki A, Kong Y, Song E, Dong W, Elvin J, Choi J, Santin A. A phase II evaluation of pembrolizumab in recurrent microsatellite instability-high (MSI-H) endometrial cancer patients with Lynch-like versus MLH-1 methylated characteristics (NCT02899793). Journal Of Clinical Oncology 2021, 39: 5523-5523. DOI: 10.1200/jco.2021.39.15_suppl.5523.Peer-Reviewed Original ResearchObjective response rateImmune checkpoint inhibitorsEndometrial cancer patientsTumor mutational burdenCancer patientsGrade 3/4 treatment-related adverse eventsSolid Tumors version 1.1Treatment-related adverse eventsSporadic tumorsPhase II pilot studyOverall survival proportionPrimary end pointResponse Evaluation CriteriaPhase II evaluationAntigen processing/presentationProcessing/presentationAdverse eventsICI resistancePrognostic significanceMechanisms of resistancePolymerase chain reactionII evaluationClinical studiesMutational burdenPatients
2020
Randomized phase II trial of carboplatin-paclitaxel compared to carboplatin-paclitaxel-trastuzumab in advanced or recurrent uterine serous carcinomas that overexpress HER2/Neu (NCT01367002): Updated survival analysis
Fader A, Roque D, Siegel E, Buza N, Hui P, Havrilesky L, Secord A, O'Malley D, Backes F, Nevadunsky N, Chambers S, Edraki B, Celano P, Bellone S, Azodi M, Ratner E, Litkouhi B, Silasi D, Schwartz P, Santin A. Randomized phase II trial of carboplatin-paclitaxel compared to carboplatin-paclitaxel-trastuzumab in advanced or recurrent uterine serous carcinomas that overexpress HER2/Neu (NCT01367002): Updated survival analysis. Gynecologic Oncology 2020, 159: 7-8. DOI: 10.1016/j.ygyno.2020.06.014.Peer-Reviewed Original Research
2019
Cervical 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
2017
SYD985, 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 patients
2009
Potential therapeutic activity of adecatumumab (MT201), a fully human monoclonal antibody, against epithelial cell adhesion molecule (EpCAM) in uterine serous papillary carcinoma
Santin A, Bellone S, El-Sahwi K, Buza N, Tavassoli F, Silasi D, Azodi M, Schwartz P, Rutherford T, Pecorelli S. Potential therapeutic activity of adecatumumab (MT201), a fully human monoclonal antibody, against epithelial cell adhesion molecule (EpCAM) in uterine serous papillary carcinoma. Journal Of Clinical Oncology 2009, 27: e16502-e16502. DOI: 10.1200/jco.2009.27.15_suppl.e16502.Peer-Reviewed Original ResearchUterine serous papillary carcinomaPrimary USPC cell linesAntibody-dependent cellular cytotoxicityUSPC cell linesNormal endometrial cellsSerous papillary carcinomaComplement-dependent cytotoxicityHuman monoclonal antibodyEpithelial cell adhesion moleculeEndometrial cellsCell adhesion moleculePapillary carcinomaTherapeutic strategiesCell linesChromium release cytotoxicity assaysFlow cytometryEpCAM expressionMonoclonal antibodiesDependent cytotoxicityAdhesion moleculesRelease cytotoxicity assayStandard treatment modalityDependent cellular cytotoxicityUterine serous carcinomaAggressive biologic behavior
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