2024
Pre-clinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition for low-grade serous ovarian cancer
McNamara B, Greenman M, Demirkiran C, Mutlu L, Hartwich T, Bellone S, Manavella D, Zipponi M, Yang-Hartwich Y, Yang K, Ratner E, Schwartz P, Santin A. Pre-clinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition for low-grade serous ovarian cancer. Gynecologic Oncology 2024, 190: s36. DOI: 10.1016/j.ygyno.2024.07.058.Peer-Reviewed Original ResearchAvutometinib plus defactinib in recurrent low-grade serous ovarian cancer: A subgroup analysis of ENGOT-OV60/GOG-3052/RAMP 201 Part A
Banerjee S, Van Nieuwenhuysen E, Santin A, Ring K, Colombo N, Thaker P, Prendergast E, Clamp A, Ray-Coquard I, Chon H, Moore K, Salinas E, Rose P, O'Malley D, Oaknin A, Monk B, Holloway R, Newman G, Moroney J, Van Gorp T, Kalbacher E, Gennigens C, Wojtynek N, Lustgarten S, Grisham R. Avutometinib plus defactinib in recurrent low-grade serous ovarian cancer: A subgroup analysis of ENGOT-OV60/GOG-3052/RAMP 201 Part A. Gynecologic Oncology 2024, 190: s55-s56. DOI: 10.1016/j.ygyno.2024.07.084.Peer-Reviewed Original ResearchSacituzumab govitecan in heavily pretreated, platinum-resistant high grade serous ovarian cancer
Greenman M, Bellone S, Demirkiran C, Hartwich T, Santin A. Sacituzumab govitecan in heavily pretreated, platinum-resistant high grade serous ovarian cancer. Gynecologic Oncology Reports 2024, 54: 101459. PMID: 39108617, PMCID: PMC11300917, DOI: 10.1016/j.gore.2024.101459.Peer-Reviewed Original ResearchHigh grade serous ovarian cancerAntibody-drug conjugatesSerous ovarian cancerSacituzumab govitecanOvarian cancerTreatment optionsPlatinum-resistant ovarian cancer patientsDose-limiting toxicityOvarian cancer patientsNovel treatment optionsPartial responseRecurrent diseaseDose reductionCancer patientsClinical trialsBackground treatmentTargeted treatmentChemotherapyTreatmentCancerDoseDiseaseOptionsTrop2PatientsTrastuzumab 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 cancerPreclinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition in low grade serous ovarian cancer
McNamara B, Demirkiran C, Hartwich T, Bellone S, Manavella D, Mutlu L, Greenman M, Zipponi M, Yang-Hartwich Y, Yang K, Ratner E, Schwartz P, Coma S, Pachter J, Santin A. Preclinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition in low grade serous ovarian cancer. Gynecologic Oncology 2024, 183: 133-140. PMID: 38493021, DOI: 10.1016/j.ygyno.2024.01.028.Peer-Reviewed Original ResearchLow grade serous ovarian carcinomaWhole-exome-sequencingGain-of-function mutationsVS-4718Preclinical efficacyLow grade serous ovarian cancerSerous ovarian cancerControl-treated miceTumor growth inhibitionWild-type KRASLoss of heterozygosityDecreased p-ERKRAF/MEK inhibitionMedian survivalOvarian cancerRecurrence rateTherapeutic optionsOral gavageTumor growthTumor samplesIn vivo activityMAPK pathway genesRAF/MEK inhibitorsP-ERKEx vivo
2023
PO004LBA/#1515 Efficacy and safety of avutometinib + defactinib in recurrent low-grade serous ovarian cancer following prior systemic therapy
Grisham R, Aghajanian C, Nieuwenhuysen E, Rodrigues M, Ring K, Santin A, Colombo N, Prendergast E, Thaker P, Moore K, Salinas E, Ray-Coquard I, Chon H, Rose P, Oaknin A, Clamp A, Gandhi M, Monk B, Holloway R, Gorp T, Fabbro M, Gennigens C, Wojtynek N, Lustgarten S, Banerjee S. PO004LBA/#1515 Efficacy and safety of avutometinib + defactinib in recurrent low-grade serous ovarian cancer following prior systemic therapy. 2023, a3-a4. DOI: 10.1136/ijgc-2023-igcs.4.Peer-Reviewed Original Research#523 Initial efficacy and safety results from ENGOT-Ov60/GOG-3052/RAMP 201: a phase 2 study of avutometinib (VS-6766) ± defactinib in recurrent low-grade serous ovarian cancer (LGSOC)
Banerjee S, Ring K, Niewenhuysen E, Fabbro M, Aghajanian C, Oaknin A, Colombo N, Santin A, Clamp A, Moore K, Rose P, David M O, Chon H, Salinas E, Prendergast E, Lustgarten S, Rodrigues M, Gennigens C, Monk B, Grisham R. #523 Initial efficacy and safety results from ENGOT-Ov60/GOG-3052/RAMP 201: a phase 2 study of avutometinib (VS-6766) ± defactinib in recurrent low-grade serous ovarian cancer (LGSOC). 2023, a20-a21. DOI: 10.1136/ijgc-2023-esgo.29.Peer-Reviewed Original ResearchInitial efficacy and safety results from ENGOT-ov60/GOG-3052/RAMP 201: A phase 2 study of avutometinib (VS-6766) ± defactinib in recurrent low-grade serous ovarian cancer (LGSOC).
Banerjee S, Ring K, Van Nieuwenhuysen E, Fabbro M, Aghajanian C, Oaknin A, Colombo N, Santin A, Clamp A, Moore K, Rose P, O'Malley D, Chon H, Salinas E, Prendergast E, Lustgarten S, Rodrigues M, Gennigens C, Monk B, Grisham R. Initial efficacy and safety results from ENGOT-ov60/GOG-3052/RAMP 201: A phase 2 study of avutometinib (VS-6766) ± defactinib in recurrent low-grade serous ovarian cancer (LGSOC). Journal Of Clinical Oncology 2023, 41: 5515-5515. DOI: 10.1200/jco.2023.41.16_suppl.5515.Peer-Reviewed Original ResearchRecurrent low-grade serous ovarian cancerLow-grade serous ovarian cancerOptimal regimenPartial responseKRAS statusOvarian cancerHigher disease control rateMost AEsMEK inhibitorsBlinded independent central reviewRAF/MEK inhibitionDisease control ratePrior systemic regimensSimilar AE profilesNew safety signalsPhase 2 studyIndependent central reviewKey inclusion criteriaSerous ovarian cancerSynergistic antitumor activityMajority of treatmentsDermatitis acneiformEvaluable patientsCombination armSystemic regimens
2018
Binimetinib (MEK162) in recurrent low-grade serous ovarian cancer resistant to chemotherapy and hormonal treatment
Han C, Bellone S, Zammataro L, Schwartz PE, Santin AD. Binimetinib (MEK162) in recurrent low-grade serous ovarian cancer resistant to chemotherapy and hormonal treatment. Gynecologic Oncology Reports 2018, 25: 41-44. PMID: 29946554, PMCID: PMC6014583, DOI: 10.1016/j.gore.2018.05.011.Peer-Reviewed Original ResearchLow-grade serous ovarian carcinomaTreatment optionsHormonal treatmentRecurrent low-grade serous ovarian cancerRecurrent low-grade serous ovarian carcinomaLow-grade serous ovarian cancerDramatic clinical responseDrug-related toxicityEffective treatment optionNew treatment optionsSerial CT scansSerous ovarian cancerSerous ovarian carcinomaMitogen-activated protein kinase inhibitorOral steroidsRECIST 1.1Clinical responseMultiple chemotherapyOvarian carcinomaTarget lesionsOvarian cancerCT scanResponse durationBinimetinibKRAS G12A novel multiple biomarker panel for the early detection of high-grade serous ovarian carcinoma
Han C, Bellone S, Siegel ER, Altwerger G, Menderes G, Bonazzoli E, Egawa-Takata T, Pettinella F, Bianchi A, Riccio F, Zammataro L, Yadav G, Marto JA, Penet MF, Levine DA, Drapkin R, Patel A, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin AD. A novel multiple biomarker panel for the early detection of high-grade serous ovarian carcinoma. Gynecologic Oncology 2018, 149: 585-591. PMID: 29572027, PMCID: PMC5986604, DOI: 10.1016/j.ygyno.2018.03.050.Peer-Reviewed Original ResearchConceptsHigh-grade serous ovarian carcinomaSerous ovarian carcinomaIL-6Ovarian cancerOvarian carcinomaE-cadHigh-grade serous ovarian adenocarcinomaEarly-stage ovarian cancerROC analysisEarly detectionMajority of patientsLethal gynecologic malignancyStage ovarian cancerOvarian cancer patientsBenign gynecologic pathologyNon-cancer controlsSerous ovarian adenocarcinomaEffective cancer screeningSerous ovarian cancerMultiple biomarker panelsFour-marker panelHigh differential gene expressionGynecologic malignanciesCA 125IL-1ra