2023
Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of AGS15E Monotherapy in Patients with Metastatic Urothelial Carcinoma
Petrylak D, Eigl B, George S, Heath E, Hotte S, Chism D, Nabell L, Picus J, Cheng S, Appleman L, Sonpavde G, Morgans A, Pourhosseini P, Wu R, Standley L, Croitoru R, Yu E. Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of AGS15E Monotherapy in Patients with Metastatic Urothelial Carcinoma. Clinical Cancer Research 2023, 30: of1-of11. PMID: 37861407, PMCID: PMC10767306, DOI: 10.1158/1078-0432.ccr-22-3627.Peer-Reviewed Original ResearchConceptsMetastatic urothelial carcinomaObjective response rateDose-limiting toxicityAntibody-drug conjugatesUrothelial carcinomaCommon treatment-emergent adverse eventsInvestigational antibody-drug conjugateTreatment-emergent adverse eventsI dose-escalation studyDose-expansion cohortsCheckpoint inhibitor therapyPhase II doseDose-escalation studyDose-proportional mannerMultiple-dose administrationBest overall responseMonomethyl auristatin ECytotoxic drug monomethyl auristatin EPrior chemotherapyAdverse eventsDose escalationInhibitor therapyPeripheral neuropathyOcular toxicityExpansion trialStudy 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 concerns
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
2020
Study 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 endpoint