2022
Study EV-103 cohort L: Evaluating perioperative enfortumab vedotin monotherapy in cis-ineligible muscle invasive bladder cancer (MIBC) (trial in progress).
Hoimes C, Flaig T, Srinivas S, Mar N, Petrylak D, O'Donnell P, Bilen M, Sasse C, Yu Y, Birrenkott M, Rosenberg J. Study EV-103 cohort L: Evaluating perioperative enfortumab vedotin monotherapy in cis-ineligible muscle invasive bladder cancer (MIBC) (trial in progress). Journal Of Clinical Oncology 2022, 40: tps587-tps587. DOI: 10.1200/jco.2022.40.6_suppl.tps587.Peer-Reviewed Original ResearchMuscle-invasive bladder cancerMetastatic urothelial carcinomaCentral pathology reviewPerioperative therapyPathology reviewMicrotubule-disrupting agent monomethyl auristatin EPathological complete response ratePelvic lymph node dissectionBlinded independent central reviewPathological downstaging rateTolerable safety profileComplete response rateOverall survival benefitDisease-free survivalEvent-free survivalHigh-risk featuresLymph node dissectionPhase 3 studyPD-L1 inhibitorsInvasive bladder cancerIndependent central reviewPlatinum-based therapyMonomethyl auristatin ECurrent standardAntibody-drug conjugatesRandomized phase II trial of gemcitabine, avelumab and carboplatin versus no neoadjuvant therapy preceding surgery for cisplatin-ineligible muscle-invasive urothelial carcinoma (MIUC): SWOG GAP trial (S2011).
Sonpavde G, Plets M, Liss M, Meeks J, Petrylak D, Cole S, McKay R, Gupta S, Hita S, Pereira T, Bangs R, Tangen C, Thompson I, Lerner S. Randomized phase II trial of gemcitabine, avelumab and carboplatin versus no neoadjuvant therapy preceding surgery for cisplatin-ineligible muscle-invasive urothelial carcinoma (MIUC): SWOG GAP trial (S2011). Journal Of Clinical Oncology 2022, 40: tps591-tps591. DOI: 10.1200/jco.2022.40.6_suppl.tps591.Peer-Reviewed Original ResearchMuscle-invasive urothelial carcinomaMuscle-invasive bladder cancerUpper tract urothelial carcinomaImmune checkpoint inhibitorsWeeks x 4 cyclesPathologic complete remissionEvent-free survivalPhase II trialUpfront surgeryUrothelial carcinomaDay 1II trialNeoadjuvant therapyOverall survivalHigh-risk upper tract urothelial carcinomaCisplatin-ineligible metastatic urothelial carcinomaNeoadjuvant cisplatin-based combination chemotherapyOpen-label phase II trialHigh grade upper tract urothelial carcinomaNeoadjuvant immune checkpoint inhibitorsRandomized phase II trialCisplatin-based combination chemotherapyCisplatin-eligible patientsMetastatic urothelial carcinomaPD-L1 inhibitors
2021
Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors: An updated analysis of EV-201 Cohort 2.
McGregor B, Balar A, Rosenberg J, Van Der Heijden M, Park H, Lee J, Kojima T, Harrison M, Heath E, Stein M, Loriot Y, Necchi A, Steinberg J, Liang S, Trowbridge J, Petrylak D, Yu E. Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors: An updated analysis of EV-201 Cohort 2. Journal Of Clinical Oncology 2021, 39: 4524-4524. DOI: 10.1200/jco.2021.39.15_suppl.4524.Peer-Reviewed Original ResearchBlinded independent central reviewObjective response rateProgression-free survivalDuration of responseComplete responsePD-1/PD-L1 inhibitorsPrimary analysisConfirmed objective response rateCisplatin-ineligible patientsMetastatic urothelial cancerMetastatic urothelial carcinomaOverall survival benefitPeripheral sensory neuropathyPlatinum-containing chemotherapyNew safety signalsPD-L1 inhibitorsIndependent central reviewPrimary tumor siteOnset of responseAntibody-drug conjugatesPrior platinumPrimary endpointRECIST 1.1Secondary endpointsAdverse eventsStudy EV-103: Update on durability results and long term outcome of enfortumab vedotin + pembrolizumab in first line locally advanced or metastatic urothelial carcinoma (la/mUC).
Friedlander T, Milowsky M, Bilen M, Srinivas S, McKay R, Flaig T, Hoimes C, Balar A, Henry E, Petrylak D, Sasse C, Kataria R, Yu Y, Carret A, Rosenberg J. Study EV-103: Update on durability results and long term outcome of enfortumab vedotin + pembrolizumab in first line locally advanced or metastatic urothelial carcinoma (la/mUC). Journal Of Clinical Oncology 2021, 39: 4528-4528. DOI: 10.1200/jco.2021.39.15_suppl.4528.Peer-Reviewed Original ResearchMicrotubule-disrupting agent monomethyl auristatin EObjective response rateMetastatic urothelial carcinomaAntibody-drug conjugatesUrothelial carcinomaCommon treatment-related adverse eventsPD-1/PD-L1 inhibitorsConfirmed objective response rateModest objective response rateTreatment-related adverse eventsCarboplatin-based regimensSafety/tolerabilityFirst-line settingOverall survival benefitPeripheral sensory neuropathyNew safety signalsPD-L1 inhibitorsLong-term outcomesImmunogenic cell deathGreater antitumor activityMonomethyl auristatin EBreakthrough therapy designationMedian DoRMedian OSMedian PFSEV-201 Cohort 2: Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors.
Balar A, McGregor B, Rosenberg J, Van Der Heijden M, Park S, Lee J, Harrison M, Heath E, Stein M, Loriot Y, Necchi A, Steinberg J, Liang S, Kim E, Trowbridge J, Campbell M, Petrylak D, Yu E. EV-201 Cohort 2: Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors. Journal Of Clinical Oncology 2021, 39: 394-394. DOI: 10.1200/jco.2021.39.6_suppl.394.Peer-Reviewed Original ResearchPD-1/L1Blinded independent central reviewObjective response rateProgression-free survivalDuration of responseOverall survivalPD-1/L1 inhibitorsPD-1/PD-L1 inhibitorsConfirmed objective response rateCisplatin-ineligible patientsECOG PS 2Metastatic urothelial cancerMetastatic urothelial carcinomaPeripheral sensory neuropathyPlatinum-containing chemotherapySevere renal impairmentPD-L1 inhibitorsIndependent central reviewPrimary tumor siteCohort 1 dataAntibody-drug conjugatesAdult ptsPrior platinumRECIST 1.1Last dose
2020
EV-201: Long-term results of enfortumab vedotin monotherapy for locally advanced or metastatic urothelial cancer previously treated with platinum and PD-1/PD-L1 inhibitors
O'Donnell P, Galsky M, Rosenberg J, Petrylak D, Balar A, McGregor B, Heath E, Yu E, Quinn D, Hahn N, Campbell M, Liang S, Steinberg J, Loriot Y. EV-201: Long-term results of enfortumab vedotin monotherapy for locally advanced or metastatic urothelial cancer previously treated with platinum and PD-1/PD-L1 inhibitors. Annals Of Oncology 2020, 31: s579-s580. DOI: 10.1016/j.annonc.2020.08.818.Peer-Reviewed Original ResearchStudy EV-103: New randomized cohort testing enfortumab vedotin as monotherapy or in combination with pembrolizumab in locally advanced or metastatic urothelial cancer.
Mar N, Friedlander T, Hoimes C, Flaig T, Bilen M, Balar A, Henry E, Srinivas S, Rosenberg J, Petrylak D, Burgess E, Merchan J, Tagawa S, Carret A, Steinberg J, Chaney M, Milowsky M. Study EV-103: New randomized cohort testing enfortumab vedotin as monotherapy or in combination with pembrolizumab in locally advanced or metastatic urothelial cancer. Journal Of Clinical Oncology 2020, 38: tps5092-tps5092. DOI: 10.1200/jco.2020.38.15_suppl.tps5092.Peer-Reviewed Original ResearchPD-1/PD-L1 inhibitorsPlatinum-containing chemotherapyMetastatic urothelial cancerPD-L1 inhibitorsRECIST v1.1Investigator assessmentUrothelial cancerMicrotubule-disrupting agent monomethyl auristatin EDay 1PD-1 inhibitor pembrolizumabActive CNS metastasesCisplatin-containing therapyFirst-line patientsPrior systemic treatmentPD-L1 statusTumor response rateMonomethyl auristatin EAntibody-drug conjugatesMeasurable diseaseCNS metastasisPrimary endpointSecondary endpointsCreatinine clearanceSystemic treatmentUncontrolled diabetesStudy 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 studyStudy EV-103: New cohorts testing enfortumab vedotin alone or in combination with pembrolizumab in muscle invasive urothelial cancer.
Hoimes C, Rosenberg J, Petrylak D, Carret A, Sasse C, Chaney M, Flaig T. Study EV-103: New cohorts testing enfortumab vedotin alone or in combination with pembrolizumab in muscle invasive urothelial cancer. Journal Of Clinical Oncology 2020, 38: tps595-tps595. DOI: 10.1200/jco.2020.38.6_suppl.tps595.Peer-Reviewed Original ResearchMuscle-invasive urothelial cancerInvasive urothelial cancerRadical cystectomyPathology reviewUrothelial cancerMicrotubule-disrupting agent monomethyl auristatin EDay 1PD-1/PD-L1 inhibitorsResponse rateInvestigational antibody-drug conjugatePathological complete response rateTreatment-related adverse eventsNeoadjuvant cisplatin-based chemotherapyCisplatin-eligible patientsPathological response rateComplete response rateFirst-line settingLymph node dissectionPD-1 inhibitorsCentral pathology reviewDisease-free survivalPhase 2 studyCisplatin-based chemotherapyPD-L1 inhibitorsMonomethyl auristatin E
2019
902O An adaptive, biomarker directed platform study in metastatic urothelial cancer (BISCAY) with durvalumab in combination with targeted therapies
Powles T, Balar A, Gravis G, Jones R, Ravaud A, Florence J, Grivas P, Petrylak D, Galsky M, Carles J, Sridhar S, Arkenau H, Carroll D, DeCesare J, Mercier F, Hodgson D, Stone J, Cosaert J, Landers D. 902O An adaptive, biomarker directed platform study in metastatic urothelial cancer (BISCAY) with durvalumab in combination with targeted therapies. Annals Of Oncology 2019, 30: v356-v357. DOI: 10.1093/annonc/mdz249.001.Peer-Reviewed Original ResearchSarah Cannon Research InstituteBristol-Myers SquibbGenentech/RocheUrothelial cancerSeattle GeneticsMonotherapy armArm BClovis OncologyRoche LaboratoriesAstellas PharmaNext-generation sequencingRoche-GenentechAdvanced urothelial cancerConclusions Combination treatmentNon-randomized controlsMetastatic urothelial cancerPD-L1 expressionKey secondary objectivePD-L1 inhibitorsTumor DNA alterationsEli LillyBavarian NordicConfirmed responsesD monotherapyOS rates