2024
Impact of exposure on outcomes with enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer.
Petrylak D, Chia Y, Yu E, Powles T, Flaig T, Loriot Y, O'Donnell P, Heath E, Kojima T, Park S, Sonpavde G, Picus J, Matsubara N, Obara W, Chudasama V, Poondru S, Harrison M, Kim E, Brancato S, Rosenberg J. Impact of exposure on outcomes with enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer. Journal Of Clinical Oncology 2024, 42: 4503-4503. DOI: 10.1200/jco.2024.42.16_suppl.4503.Peer-Reviewed Original ResearchMetastatic urothelial cancerEnfortumab vedotinDose modificationEV exposureUrothelial cancerPre-dose samplesAssociated with lower riskPopulation PK modelLikelihood of responseEV-201Median PFSOS benefitOS outcomesDose reductionExposure quartilesExposure-responsePK assessmentEfficacy outcomesSafety profilePeripheral neuropathySkin reactionsPK modelLow riskSafety outcomesDose response
2023
Safety analysis by UGT1A1 status of TROPHY-U-01 cohort 1, a phase 2 study of sacituzumab govitecan (SG) in patients (pts) with metastatic urothelial cancer (mUC) who progressed after platinum (PT)-based chemotherapy and a checkpoint inhibitor (CPI).
Loriot Y, Petrylak D, Rezazadeh A, Flechon A, Jain R, Gupta S, Bupathi M, Beuzeboc P, Palmbos P, Kyriakopoulos C, Pouessel D, Sternberg C, Tonelli J, Sierecki M, Zhou H, Grivas P, Barthelemy P, Balar A, Tagawa S. Safety analysis by UGT1A1 status of TROPHY-U-01 cohort 1, a phase 2 study of sacituzumab govitecan (SG) in patients (pts) with metastatic urothelial cancer (mUC) who progressed after platinum (PT)-based chemotherapy and a checkpoint inhibitor (CPI). Journal Of Clinical Oncology 2023, 41: 4514-4514. DOI: 10.1200/jco.2023.41.16_suppl.4514.Peer-Reviewed Original ResearchObjective response rateMetastatic urothelial cancerSacituzumab govitecanUGT1A1 statusCheckpoint inhibitorsOverall survivalSafety profileSafety outcomesECOG PS 0Treatment-related discontinuationsManageable safety profileMedian overall survivalPhase 2 studyChronic kidney diseasePrior reportsCoronary artery diseaseAdverse event occurrenceAntibody-drug conjugatesBaseline comorbiditiesDose interruptionPrimary endpointPrior therapyRECIST 1.1PS 0Adverse eventsStudy EV-103: Neoadjuvant treatment with enfortumab vedotin monotherapy in cisplatin-ineligible patients (pts) with muscle invasive bladder cancer (MIBC): Updated results for Cohort H.
Flaig T, Rosenberg J, Hoimes C, O'Donnell P, Mar N, Gourdin T, Henry S, Bilen M, George S, Barata P, Srinivas S, Rao S, Assikis V, Burgess E, Ramamurthy C, Haas G, Lukas J, Mildiner-Earley S, Yu Y, Petrylak D. Study EV-103: Neoadjuvant treatment with enfortumab vedotin monotherapy in cisplatin-ineligible patients (pts) with muscle invasive bladder cancer (MIBC): Updated results for Cohort H. Journal Of Clinical Oncology 2023, 41: 4595-4595. DOI: 10.1200/jco.2023.41.16_suppl.4595.Peer-Reviewed Original ResearchMuscle-invasive bladder cancerEvent-free survivalPhase 1b/2 studyPathological complete responseCancer-related therapyEV treatmentUrothelial cancerSafety profilePD-1/L1 inhibitorsMedian event-free survivalPelvic lymph node dissectionAdvanced urothelial cancerAntitumor activityCisplatin-ineligible patientsManageable safety profileNeoadjuvant treatment optionsOngoing phase 2Pathological downstaging ratePts underwent surgeryTolerable safety profileCentral pathology reviewKey secondary endpointLymph node dissectionPhase 3 studyInvasive bladder cancerStudy EV-103 dose escalation/cohort A: Long-term outcome of enfortumab vedotin + pembrolizumab in first-line (1L) cisplatin-ineligible locally advanced or metastatic urothelial carcinoma (la/mUC) with nearly 4 years of follow-up.
Gupta S, Rosenberg J, McKay R, Flaig T, Petrylak D, Hoimes C, Friedlander T, Bilen M, Srinivas S, Burgess E, Merchan J, Tagawa S, Brown J, Yu Y, Carret A, Wirtz H, Guseva M, Homet Moreno B, Milowsky M. Study EV-103 dose escalation/cohort A: Long-term outcome of enfortumab vedotin + pembrolizumab in first-line (1L) cisplatin-ineligible locally advanced or metastatic urothelial carcinoma (la/mUC) with nearly 4 years of follow-up. Journal Of Clinical Oncology 2023, 41: 4505-4505. DOI: 10.1200/jco.2023.41.16_suppl.4505.Peer-Reviewed Original ResearchAdverse eventsCohort ASafety profileSkin reactionsPD-1/PD-L1 inhibitor monotherapyCommon treatment-emergent adverse eventsCommon treatment-related adverse eventsOngoing phase 3 studiesPD-L1 inhibitor monotherapySystemic anti-cancer therapyTreatment-emergent adverse eventsTreatment-related adverse eventsCarboplatin-based chemotherapyCarboplatin-based therapyCisplatin-ineligible patientsManageable safety profilePhase 1b/2 studySafety/tolerabilityKey secondary endpointMetastatic urothelial carcinomaAvailable therapeutic optionsPhase 3 studySevere skin reactionsLong-term outcomesNew safety concernsPrimary analysis of TROPHY-U-01 cohort 2, a phase 2 study of sacituzumab govitecan (SG) in platinum (PT)-ineligible patients (pts) with metastatic urothelial cancer (mUC) that progressed after prior checkpoint inhibitor (CPI) therapy.
Petrylak D, Tagawa S, Jain R, Bupathi M, Balar A, Rezazadeh A, George S, Palmbos P, Nordquist L, Davis N, Ramamurthy C, Sternberg C, Loriot Y, Agarwal N, Park C, Tonelli J, Vance M, Zhou H, Grivas P. Primary analysis of TROPHY-U-01 cohort 2, a phase 2 study of sacituzumab govitecan (SG) in platinum (PT)-ineligible patients (pts) with metastatic urothelial cancer (mUC) that progressed after prior checkpoint inhibitor (CPI) therapy. Journal Of Clinical Oncology 2023, 41: 520-520. DOI: 10.1200/jco.2023.41.6_suppl.520.Peer-Reviewed Original ResearchTreatment-related adverse eventsMetastatic urothelial cancerObjective response rateProgression-free survivalDuration of responseManageable safety profilePrior anticancer therapyMedian overall survivalCPI therapySacituzumab govitecanOverall survivalCentral reviewMedian timeSafety profileTreatment optionsCohort 2Primary analysisResponse rateAnti-Trop-2 antibodyMedian DORMedian progression-free survivalAccelerated FDA approvalCheckpoint inhibitor therapyECOG PS 0ECOG PS 1
2021
The efficacy of enzalutamide (ENZA) plus androgen deprivation therapy (ADT) on bone oligometastatic hormone-sensitive prostate cancer: A post hoc analysis of ARCHES.
Armstrong A, Iguchi T, Azad A, Villers A, Alekseev B, Petrylak D, Szmulewitz R, Alcaraz A, Shore N, Holzbeierlein J, Gomez-Veiga F, Rosbrook B, Zohren F, Haas G, Gourgioti G, El-Chaar N, Stenzl A. The efficacy of enzalutamide (ENZA) plus androgen deprivation therapy (ADT) on bone oligometastatic hormone-sensitive prostate cancer: A post hoc analysis of ARCHES. Journal Of Clinical Oncology 2021, 39: 5071-5071. DOI: 10.1200/jco.2021.39.15_suppl.5071.Peer-Reviewed Original ResearchMetastatic hormone-sensitive prostate cancerAndrogen deprivation therapyEfficacy of enzalutamideHormone-sensitive prostate cancerBone metastasesTreatment armsProstate cancerOligometastatic hormone-sensitive prostate cancerPrior docetaxel chemotherapySecondary clinical outcomesDeprivation therapyEfficacy outcomesRadiographic progressionSecondary endpointsBaseline characteristicsDisease volumeDocetaxel chemotherapyMetastatic burdenPolymetastatic diseaseArch studyClinical outcomesCentral reviewClinical benefitSafety profilePlaceboEfficacy of enzalutamide (ENZA) plus androgen deprivation therapy (ADT) in men with de novo (M1) metastatic hormone-sensitive prostate cancer (mHSPC) versus progression to mHSPC (M0): Post hoc analysis of the phase III ARCHES trial.
Azad A, Villers A, Alekseev B, Szmulewitz R, Alcaraz A, Shore N, Petrylak D, Holzbeierlein J, Gomez-Veiga F, Rosbrook B, Zohren F, Lee H, Haas G, Iguchi T, Stenzl A, Armstrong A. Efficacy of enzalutamide (ENZA) plus androgen deprivation therapy (ADT) in men with de novo (M1) metastatic hormone-sensitive prostate cancer (mHSPC) versus progression to mHSPC (M0): Post hoc analysis of the phase III ARCHES trial. Journal Of Clinical Oncology 2021, 39: 102-102. DOI: 10.1200/jco.2021.39.6_suppl.102.Peer-Reviewed Original ResearchMetastatic hormone-sensitive prostate cancerEfficacy of enzalutamideAndrogen deprivation therapyDe novo metastatic hormone-sensitive prostate cancerM1 diseaseInitial diagnosisProstate-specific antigenSecondary endpointsDisease volumeTreatment armsHormone-sensitive prostate cancerProgression-free survival eventsPrior docetaxel useKey secondary endpointNew antineoplastic therapiesDeprivation therapyDocetaxel usePrior docetaxelEfficacy outcomesPrimary endpointPSA progressionBaseline characteristicsObjective responseClinical benefitSafety profile
2020
Early results of TROPHY-U-01 Cohort 2: Sacituzumab govitecan (SG) in platinum-ineligible patients (pts) with metastatic urothelial cancer (mUC) who progressed after prior checkpoint inhibitor (CPI) therapy.
Petrylak D, Tagawa S, Jain R, Bupathi M, Balar A, Rezazadeh A, George S, Palmbos P, Nordquist L, Davis N, Vogelzang N, Ramamurthy C, Sternberg C, Loriot Y, Agarwal N, Hong Q, Gladden A, Kanwal C, Goswami T, Grivas P. Early results of TROPHY-U-01 Cohort 2: Sacituzumab govitecan (SG) in platinum-ineligible patients (pts) with metastatic urothelial cancer (mUC) who progressed after prior checkpoint inhibitor (CPI) therapy. Journal Of Clinical Oncology 2020, 38: 5027-5027. DOI: 10.1200/jco.2020.38.15_suppl.5027.Peer-Reviewed Original ResearchMetastatic urothelial cancerOverall response rateTreatment-related AEsSacituzumab govitecanCPI therapySafety profileCohort 2Anti-Trop-2 antibodyFirst-line metastatic settingECOG PS 0Epithelial cell surface antigenPlatinum-ineligible patientsPrior treatment linesTreatment-related deathsCheckpoint inhibitor therapyManageable safety profilePhase 2 trialProgression-free survivalInterstitial lung diseaseDuration of responseMajority of ptsCell surface antigensAdvanced UCCPI treatmentFebrile neutropeniaStudy EV-103: Preliminary durability results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma.
Rosenberg J, Flaig T, Friedlander T, Milowsky M, Srinivas S, Petrylak D, Merchan J, Bilen M, Carret A, Yuan N, Sasse C, Hoimes C. Study EV-103: Preliminary durability results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma. Journal Of Clinical Oncology 2020, 38: 441-441. DOI: 10.1200/jco.2020.38.6_suppl.441.Peer-Reviewed Original ResearchMetastatic urothelial carcinomaAdverse eventsUrothelial carcinomaDay 1Common treatment-emergent adverse eventsPD-1/PD-L1 inhibitorsTreatment-emergent adverse eventsSafety/tolerabilityFirst-line settingManageable safety profilePeripheral sensory neuropathyPD-L1 statusPD-L1 inhibitorsMedian DoRMedian PFSRECIST v1.1Primary endpointLiver metastasesStandard therapyPD-L1Sensory neuropathySafety profilePlatinum chemotherapyHigh patientMulticohort studyFORT-1: Phase II/III study of rogaratinib versus chemotherapy (CT) in patients (pts) with locally advanced or metastatic urothelial carcinoma (UC) selected based on FGFR1/3 mRNA expression.
Quinn D, Petrylak D, Bellmunt J, Necchi A, Gurney H, Lee J, Van Der Heijden M, Rosenbaum E, Penel N, Pang S, Li J, Garcia del Muro X, Joly F, Papai Z, Ellinghaus P, Lu C, Nakajima K, Ishida T, Nishiyama H, Sternberg C. FORT-1: Phase II/III study of rogaratinib versus chemotherapy (CT) in patients (pts) with locally advanced or metastatic urothelial carcinoma (UC) selected based on FGFR1/3 mRNA expression. Journal Of Clinical Oncology 2020, 38: 489-489. DOI: 10.1200/jco.2020.38.6_suppl.489.Peer-Reviewed Original ResearchMetastatic urothelial carcinomaUrothelial carcinomaPhase II/III studyMedian progression-free survivalTreatment-emergent adverse eventsMuscle-invasive urothelial carcinomaPhase II/IIIDisease control rateOpen-label studyProgression-free survivalStage IV diseaseAcceptable safety profileUrinary tract infectionDNA alterationsStage IIIBIII studyPrior immunotherapyStandard chemotherapyTract infectionsAdverse eventsMedian agePlatinum chemotherapySafety profileControl rateSubgroup analysis
2009
Final results of a phase I study of oral belinostat (PXD101) in patients with solid tumors
Kelly W, DeBono J, Blumenschein G, Lassen U, Zain J, O'Connor O, Foss F, Tjornelund J, Fagerberg J, Petrylak D. Final results of a phase I study of oral belinostat (PXD101) in patients with solid tumors. Journal Of Clinical Oncology 2009, 27: 3531-3531. DOI: 10.1200/jco.2009.27.15_suppl.3531.Peer-Reviewed Original ResearchAdverse eventsFrequent related adverse eventsRelated adverse eventsMedian age 60Histone deacetylase inhibitorsMajor cancer typesMultiple tumor typesDaily x5Overall tolerabilityDose escalationQTc prolongationSafety profilePreclinical activityClinical activitySerial ECGsDay 1Age 60Solid tumorsTumor typesDeacetylase inhibitorsCohort 2aFurther evaluationPharmacokineticsCancer typesMultiple scheduleFinal results of a phase I study of oral belinostat (PXD101) in patients with lymphoma
Zain J, Foss F, Kelly W, DeBono J, Petrylak D, Narwal A, Neylon E, Blumenschein G, Lassen U, O'Connor O. Final results of a phase I study of oral belinostat (PXD101) in patients with lymphoma. Journal Of Clinical Oncology 2009, 27: 8580-8580. DOI: 10.1200/jco.2009.27.15_suppl.8580.Peer-Reviewed Original ResearchNon-Hodgkin lymphomaHodgkin's diseaseDose escalationTumor shrinkageSolid tumorsIntra-patient dose escalationRefractory non-Hodgkin lymphomaPhase IAcceptable organ functionEarly tumor shrinkageMedian age 51Frequent adverse eventsPossible dose escalationMantle cell lymphomaHistone deacetylase inhibitorsEvaluable diseaseLeg DVTPrior regimensQ3w scheduleStable diseaseAdverse eventsDaily doseSafety profileCohort C.Preclinical activity
2006
A Phase I Trial of Pox PSA vaccines (PROSTVAC®-VF) with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules (TRICOM™) in Patients with Prostate Cancer
DiPaola R, Plante M, Kaufman H, Petrylak D, Israeli R, Lattime E, Manson K, Schuetz T. A Phase I Trial of Pox PSA vaccines (PROSTVAC®-VF) with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules (TRICOM™) in Patients with Prostate Cancer. Journal Of Translational Medicine 2006, 4: 1. PMID: 16390546, PMCID: PMC1360095, DOI: 10.1186/1479-5876-4-1.Peer-Reviewed Original ResearchProstate-specific antigenSerious adverse eventsAdverse eventsProstate cancerB7-1ICAM-1Co-stimulatory molecules B7-1Mean prostate-specific antigenRecombinant vaccinia virus vaccineAndrogen-independent prostate cancerFurther phase IIPreliminary clinical activityInjection site reactionsPhase I trialVaccinia virus vaccineCo-stimulatory moleculesIndependent prostate cancerFeasible therapeutic approachRecombinant fowlpox virusStable diseaseMetastatic diseaseProgressive diseaseI trialTherapeutic vaccinesSafety profile
2000
A Phase II Pilot Study of KW-2189 in Patients with Advanced Renal Cell Carcinoma
Small E, Figlin R, Petrylak D, Vaughn D, Sartor O, Horak I, Pincus R, Kremer A, Bowden C. A Phase II Pilot Study of KW-2189 in Patients with Advanced Renal Cell Carcinoma. Investigational New Drugs 2000, 18: 193-198. PMID: 10857997, DOI: 10.1023/a:1006386115312.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaMetastatic renal cell carcinomaCell carcinomaOpen-label phase II trialCommon drug-related toxicitiesAdvanced renal cell carcinomaPhase II pilot studyNon-hematologic toxicitiesPhase II trialDrug-related toxicityPredictable safety profileReversible myelosuppressionII trialObjective responseSafety profileDisease progressionModerate fatigueWeek 6PatientsSignificant toxicityCarcinomaPilot studyAntitumor potencyWater-soluble analogueCycle 1