2023
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.
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 concernsSafety 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 eventsEnfortumab vedotin (EV) with or without pembrolizumab (P) in patients (pts) who are cisplatin-ineligible with previously untreated locally advanced or metastatic urothelial cancer (la/mUC): Additional 3-month follow-up on cohort K data.
Friedlander T, Milowsky M, O'Donnell P, Petrylak D, Hoimes C, Flaig T, Mar N, Moon H, McKay R, Bilen M, Borchiellini D, Iafolla M, Carret A, Yu Y, Guseva M, Kataria R, Rosenberg J. Enfortumab vedotin (EV) with or without pembrolizumab (P) in patients (pts) who are cisplatin-ineligible with previously untreated locally advanced or metastatic urothelial cancer (la/mUC): Additional 3-month follow-up on cohort K data. Journal Of Clinical Oncology 2023, 41: 4568-4568. DOI: 10.1200/jco.2023.41.16_suppl.4568.Peer-Reviewed Original ResearchProgression-free survivalDisease control rateDuration of responseMedian DORMedian progression-free survivalBlinded independent central reviewOverall survivalPFS rateAdverse eventsOS ratesSkin reactionsTreatment-emergent adverse eventsTreatment-related adverse eventsFirst-line treatment optionManageable safety profileObjective response ratePD-1 inhibitorsMetastatic urothelial cancerSevere skin reactionsIndependent central reviewNew safety concernsHigh unmet needImmunogenic cell deathRECIST v1.1Primary endpointStudy 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 cancerEnfortumab vedotin (EV) alone or in combination with pembrolizumab (P) in previously untreated cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer (la/mUC): Subgroup analyses of confirmed objective response rate (cORR) from EV-103 cohort K.
O'Donnell P, Rosenberg J, Hoimes C, Petrylak D, Milowsky M, McKay R, Srinivas S, Friedlander T, Ramamurthy C, Bilen M, Burgess E, Mar N, Moon H, Geynisman D, George S, Carret A, Yu Y, Guseva M, Moreno B, Flaig T. Enfortumab vedotin (EV) alone or in combination with pembrolizumab (P) in previously untreated cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer (la/mUC): Subgroup analyses of confirmed objective response rate (cORR) from EV-103 cohort K. Journal Of Clinical Oncology 2023, 41: 499-499. DOI: 10.1200/jco.2023.41.6_suppl.499.Peer-Reviewed Original ResearchLiver metastasesDay 1Disease sitesPD-L1 expression statusBlinded independent central reviewAppropriate dose modificationCisplatin-ineligible patientsManageable safety profileMetastatic urothelial cancerObjective response rateECOG PS scorePhase 3 trialPre-specified subgroupsPrimary disease siteDuration of responseIndependent central reviewMetastatic disease sitesHigh unmet needECOG PSMedian DoRRECIST v1.1Untreated LAOverall cohortPrimary endpointSecondary endpointsPrimary analysis of TROPHY-U-01 cohort 3, a phase 2 study of sacituzumab govitecan (SG) in combination with pembrolizumab (Pembro) in patients (pts) with metastatic urothelial cancer (mUC) that progressed after platinum (PT)-based therapy.
Grivas P, Pouessel D, Park C, Barthelemy P, Bupathi M, Petrylak D, Agarwal N, Gupta S, Flechon A, Ramamurthy C, Davis N, Recio-Boiles A, Sternberg C, Bhatia A, Pichardo C, Sierecki M, Tonelli J, Zhou H, Tagawa S, Loriot Y. Primary analysis of TROPHY-U-01 cohort 3, a phase 2 study of sacituzumab govitecan (SG) in combination with pembrolizumab (Pembro) in patients (pts) with metastatic urothelial cancer (mUC) that progressed after platinum (PT)-based therapy. Journal Of Clinical Oncology 2023, 41: 518-518. DOI: 10.1200/jco.2023.41.6_suppl.518.Peer-Reviewed Original ResearchTreatment-related adverse eventsObjective response rateMetastatic urothelial cancerProgression-free survivalDuration of responseHigher objective response rateSacituzumab govitecanCentral reviewCohort 3Primary analysisAnti-Trop-2 antibodyMedian DORMedian progression-free survivalAccelerated FDA approvalClinical benefit rateECOG PS 0ECOG PS 1Manageable safety profileTreatment-related deathsNew safety signalsPhase 2 studyG-CSF useAnti-cancer therapyMedian OSSystemic steroidsPrimary 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
2022
TROPHY-U-01 Cohort 3: Sacituzumab govitecan (SG) in combination with pembrolizumab (Pembro) in patients (pts) with metastatic urothelial cancer (mUC) who progressed after platinum (PLT)-based regimens.
Grivas P, Pouessel D, Park C, Barthélémy P, Bupathi M, Petrylak D, Agarwal N, Flechon A, Ramamurthy C, Davis N, Recio-Boiles A, Tagawa S, Sternberg C, Bhatia A, Pichardo C, Goswami T, Loriot Y. TROPHY-U-01 Cohort 3: Sacituzumab govitecan (SG) in combination with pembrolizumab (Pembro) in patients (pts) with metastatic urothelial cancer (mUC) who progressed after platinum (PLT)-based regimens. Journal Of Clinical Oncology 2022, 40: 434-434. DOI: 10.1200/jco.2022.40.6_suppl.434.Peer-Reviewed Original ResearchObjective response rateTreatment-emergent adverse eventsMetastatic urothelial cancerInvestigator-assessed objective response ratePhase 2 trialProgression-free survivalSacituzumab govitecanCheckpoint inhibitorsEastern Cooperative Oncology Group performance status 0Most common treatment-emergent adverse eventsCommon treatment-emergent adverse eventsSolid Tumors version 1.1Long-term disease controlBlinded independent central reviewAntigen 2 antibodiesClinical benefit rateECOG PS 1Manageable safety profileMedian overall survivalPerformance status 0Phase 2 doseTreatment-related AEsTreatment-related deathsTreatment-related gradeNew safety signals
2021
First-in-human, phase I study of PF-06753512, a vaccine-based immunotherapy regimen (PrCa VBIR), in biochemical relapse (BCR) and metastatic castration-resistant prostate cancer (mCRPC).
Autio K, Higano C, Nordquist L, Appleman L, Zhang T, Zhu X, Babiker H, Vogelzang N, Prasad S, Schweizer M, Billotte S, Binder J, Cavazos N, Li R, Chan K, Cho H, Dermyer M, Hollingsworth R, Kern K, Petrylak D. First-in-human, phase I study of PF-06753512, a vaccine-based immunotherapy regimen (PrCa VBIR), in biochemical relapse (BCR) and metastatic castration-resistant prostate cancer (mCRPC). Journal Of Clinical Oncology 2021, 39: 2612-2612. DOI: 10.1200/jco.2021.39.15_suppl.2612.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerTreatment-related adverse eventsImmune checkpoint inhibitorsBiochemical relapseImmune responseCastration-resistant prostate cancerPhase INovel hormone therapyAntitumor activityManageable safety profileObjective tumor responsePD-1 antibodyAntigen-specific immunityProstate-specific membrane antigenAndrogen-sensitive diseaseReplication-deficient adenoviral vectorAnti-tumor activityStem cell antigenPC-associated antigensNoticeable antitumor activityAntibody tremelimumabExpansion doseCheckpoint inhibitorsImmunotherapy regimenAdverse events
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: 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: Durability results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma. Journal Of Clinical Oncology 2020, 38: 5044-5044. DOI: 10.1200/jco.2020.38.15_suppl.5044.Peer-Reviewed Original ResearchMetastatic urothelial carcinomaPD-1/PD-L1 inhibitorsPD-L1 inhibitorsAdverse eventsUrothelial carcinomaDay 1Common treatment-emergent adverse eventsTreatment-emergent adverse eventsCisplatin-ineligible patientsSafety/tolerabilityFirst-line settingManageable safety profilePeripheral sensory neuropathyPlatinum-containing chemotherapyTumor response ratePD-L1 statusMedian DoRMedian OSMedian PFSPFS ratesRECIST v1.1Primary endpointLiver metastasesOS ratesPD-L1Study 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 study
2019
901O EV-103: Initial results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma
Hoimes C, Rosenberg J, Srinivas S, Petrylak D, Milowsky M, Merchan J, Bilen M, Gupta S, Carret A, Yuan N, Melhem-Bertrandt A, Flaig T. 901O EV-103: Initial results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma. Annals Of Oncology 2019, 30: v356. DOI: 10.1093/annonc/mdz249.Peer-Reviewed Original ResearchBristol-Myers SquibbMetastatic urothelial carcinomaAdverse eventsSeattle GeneticsUrothelial carcinomaDay 1Common treatment-emergent adverse eventsEli LillyTreatment-emergent adverse eventsDose-escalation cohortsGenentech/RocheImmune-mediated eventsPhase 1b studyPost-baseline scanSafety/tolerabilityManageable safety profileSystemic steroid treatmentKey secondary objectiveStandard of careBavarian NordicFortress BiotechMonotherapy dataRECIST 1.1Encouraging efficacyPrimary endpointEV-201: Results of enfortumab vedotin monotherapy for locally advanced or metastatic urothelial cancer previously treated with platinum and immune checkpoint inhibitors.
Petrylak D, Balar A, O'Donnell P, McGregor B, Heath E, Yu E, Galsky M, Hahn N, Gartner E, Pinelli J, Melhem-Bertrandt A, Rosenberg J. EV-201: Results of enfortumab vedotin monotherapy for locally advanced or metastatic urothelial cancer previously treated with platinum and immune checkpoint inhibitors. Journal Of Clinical Oncology 2019, 37: 4505-4505. DOI: 10.1200/jco.2019.37.18_suppl.lba4505.Peer-Reviewed Original ResearchTreatment-related AEsMetastatic urothelial cancerCheckpoint inhibitorsDuration of responseLiver metastasesUrothelial cancerCohort 1Common treatment-related AEsBlinded independent central reviewImmune checkpoint inhibitorsManageable safety profilePlatinum-containing chemotherapyPhase 1 trialLimited treatment optionsIndependent central reviewHigh unmet needTwo-cohort studyMUC patientsPrior chemotherapyPrior platinumRECIST 1.1Primary endpointSecondary endpointsPulmonary infectionPeripheral neuropathy