2023
First-in-human, phase 1 study of PF-06753512, a vaccine-based immunotherapy regimen (VBIR), in non-metastatic hormone-sensitive biochemical recurrence 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, Madan R, Billotte S, Cavazos N, Bogg O, Li R, Chan K, Cho H, Kaneda M, Wang I, Zheng J, Tang S, Hollingsworth R, Kern K, Petrylak D. First-in-human, phase 1 study of PF-06753512, a vaccine-based immunotherapy regimen (VBIR), in non-metastatic hormone-sensitive biochemical recurrence and metastatic castration-resistant prostate cancer (mCRPC). Journal For ImmunoTherapy Of Cancer 2023, 11: e005702. PMID: 36948505, PMCID: PMC10040068, DOI: 10.1136/jitc-2022-005702.Peer-Reviewed Original ResearchConceptsMetastatic castration-resistant prostate cancerAndrogen deprivation therapyRadiographic progression-free survivalCastration-resistant prostate cancerPhase 1 studyBiochemical recurrenceProstate cancerImmunotherapy regimenMedian durationDose escalationMedian radiographic progression-free survivalAntigen-specific T cell responsesImmune-related adverse eventsRecommended phase 2 doseSpecific T cell responsesPhase 2 doseImmune checkpoint inhibitorsModest antitumor activityObjective response rateProgression-free survivalAntigen-specific immunityT cell responsesInfluenza-like illnessSignificant side effectsDeprivation therapy
2020
MEDI3726, a prostate-specific membrane antigen (PSMA)-targeted antibody-drug conjugate (ADC) in mCRPC after failure of abiraterone or enzalutamide.
De Bono J, Fleming M, Wang J, Cathomas R, Williams M, Bothos J, Balic K, Cho S, Martinez P, Petrylak D. MEDI3726, a prostate-specific membrane antigen (PSMA)-targeted antibody-drug conjugate (ADC) in mCRPC after failure of abiraterone or enzalutamide. Journal Of Clinical Oncology 2020, 38: 99-99. DOI: 10.1200/jco.2020.38.6_suppl.99.Peer-Reviewed Original ResearchDrug-related adverse eventsAdverse eventsAntibody-drug conjugatesMedian progression-free survivalComposite response rateGrade 3 thrombocytopeniaMedian overall survivalProgression-free survivalTaxane-based therapyPhase 1 studyDuration of responseProstate-specific membrane antigenDrug-related deathsTumor cell countPrior regimensRECIST v1.1Grade 3/4PSA decreaseStarting doseOverall survivalUnacceptable toxicityMedian ageDose escalationAntidrug antibodiesEfficacy analysis
2019
895TiP A phase I study of AMG 160, a half-life extended bispecific T cell engager (HLE BiTE) immuno-oncology therapy targeting PSMA, in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)
Tran B, Kouros-Mehr H, Fermin A, Horvath L, Roncolato F, Rettig M, Dorff T, Tagawa S, Subudhi S, Antonarakis E, Armstrong A, Petrylak D, Fizazi K, Salvati M, Scher H. 895TiP A phase I study of AMG 160, a half-life extended bispecific T cell engager (HLE BiTE) immuno-oncology therapy targeting PSMA, in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Annals Of Oncology 2019, 30: v353. DOI: 10.1093/annonc/mdz248.052.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerProstate-specific membrane antigenBristol-Myers SquibbPreliminary antitumor activityImmuno-oncology therapiesProstate cancerAntitumor activitySanofi-AventisCentral nervous system metastasesCastration-resistant prostate cancerBoehringer IngelheimContinuous androgen deprivation therapyEli LillySeattle GeneticsActive autoimmune diseaseGenentech/RochePFS/OSPhase 2 doseRECIST 1.1 criteriaTaxane-based regimensAndrogen deprivation therapyNervous system metastasesT effector cellsPhase 1 studyDuration of responseEV-103: Enfortumab vedotin plus pembrolizumab and/or chemotherapy for locally advanced or metastatic urothelial cancer.
Hoimes C, Rosenberg J, Petrylak D, Carret A, Melhem-Bertrandt A, Flaig T. EV-103: Enfortumab vedotin plus pembrolizumab and/or chemotherapy for locally advanced or metastatic urothelial cancer. Journal Of Clinical Oncology 2019, 37: tps4593-tps4593. DOI: 10.1200/jco.2019.37.15_suppl.tps4593.Peer-Reviewed Original ResearchMetastatic urothelial cancerCheckpoint inhibitorsDay 1Urothelial cancerCombination therapyMicrotubule-disrupting agent monomethyl auristatin EInvestigational antibody-drug conjugateFirst-line cisplatinPlatinum-containing regimenDisease control rateImmune checkpoint inhibitorsPhase 1b trialPhase 1 studyDuration of responseEnhanced immune responseMonomethyl auristatin EAntibody-drug conjugatesDose expansionResponse durabilityControl rateDisease progressionImmune responseAuristatin EResponse rateNectin-4
2018
Updated results from the enfortumab vedotin phase 1 (EV-101) study in patients with metastatic urothelial cancer (mUC).
Rosenberg J, Sridhar S, Zhang J, Smith D, Ruether J, Flaig T, Baranda J, Lang J, Plimack E, Sangha R, Heath E, Merchan J, Quinn D, Srinivas S, Milowsky M, Wu C, Gartner E, Melhem-Bertrandt A, Petrylak D. Updated results from the enfortumab vedotin phase 1 (EV-101) study in patients with metastatic urothelial cancer (mUC). Journal Of Clinical Oncology 2018, 36: 4504-4504. DOI: 10.1200/jco.2018.36.15_suppl.4504.Peer-Reviewed Original ResearchEV-201 study: A single-arm, open-label, multicenter study of enfortumab vedotin for treatment of patients with locally advanced or metastatic urothelial cancer who previously received immune checkpoint inhibitor therapy.
Rosenberg J, Heath E, O'Donnell P, Hahn N, Balar A, Gartner E, Melhem-Bertrandt A, Petrylak D. EV-201 study: A single-arm, open-label, multicenter study of enfortumab vedotin for treatment of patients with locally advanced or metastatic urothelial cancer who previously received immune checkpoint inhibitor therapy. Journal Of Clinical Oncology 2018, 36: tps542-tps542. DOI: 10.1200/jco.2018.36.6_suppl.tps542.Peer-Reviewed Original ResearchObjective response rateMetastatic urothelial cancerCheckpoint inhibitorsUrothelial cancerMicrotubule-disrupting agent monomethyl auristatin EMulticenter phase 2 studyOngoing phase 1 studiesImmune checkpoint inhibitor therapyAntitumor activityCheckpoint inhibitor therapyDisease control ratePhase 2 doseSafety/tolerabilityTreatment-related AEsImmune checkpoint inhibitorsPhase 2 studyMajority of patientsPhase 1 studyUrinary tract infectionTreatment of patientsTransitional cell carcinomaAssessment of durationMonomethyl auristatin EWarrants further investigationAntibody-drug conjugatesEV-103 study: A phase 1b dose-escalation and dose-expansion study of enfortumab vedotin in combination with immune checkpoint inhibitor (CPI) therapy for treatment of patients with locally advanced or metastatic urothelial cancer.
Hoimes C, Petrylak D, Flaig T, Carret A, Melhem-Bertrandt A, Rosenberg J. EV-103 study: A phase 1b dose-escalation and dose-expansion study of enfortumab vedotin in combination with immune checkpoint inhibitor (CPI) therapy for treatment of patients with locally advanced or metastatic urothelial cancer. Journal Of Clinical Oncology 2018, 36: tps532-tps532. DOI: 10.1200/jco.2018.36.6_suppl.tps532.Peer-Reviewed Original ResearchObjective response rateMicrotubule-disrupting agent monomethyl auristatin ECheckpoint inhibitorsMetastatic urothelial cancerAntibody-drug conjugatesUrothelial cancerFirst-line cisplatin-based chemotherapyResponse rateOngoing phase 1 studiesImmune checkpoint inhibitor therapyCheckpoint inhibitor therapyDisease control rateDose-expansion studyFirst-line cisplatinPhase 1b studyPlatinum-containing regimenImmune checkpoint inhibitorsCisplatin-based chemotherapyPhase 1 studyTumor immune infiltrationDuration of responseMMAE antibody–drug conjugatesTreatment of patientsTransitional cell carcinomaPhase 1 study resultsEnfortumab vedotin (EV) in patients (Pts) with metastatic urothelial carcinoma (mUC) with prior checkpoint inhibitor (CPI) failure: A prospective cohort of an ongoing phase 1 study.
Petrylak D, Smith D, Flaig T, Zhang J, Sridhar S, Ruether J, Plimack E, Merchan J, Quinn D, Kilari D, Srinivas S, Baranda J, Lang J, Milowsky M, Galsky M, Spira A, Gartner E, Wu C, Melhem-Bertrandt A, Rosenberg J. Enfortumab vedotin (EV) in patients (Pts) with metastatic urothelial carcinoma (mUC) with prior checkpoint inhibitor (CPI) failure: A prospective cohort of an ongoing phase 1 study. Journal Of Clinical Oncology 2018, 36: 431-431. DOI: 10.1200/jco.2018.36.6_suppl.431.Peer-Reviewed Original ResearchMetastatic urothelial carcinomaOngoing phase 1 studiesPhase 1 studyLiver metastasesEvaluable ptsDisease progressionNectin-4High unmet medical needPhase 2 dosePost-baseline scanAntitumor activityMedian treatment durationPhase 2 studyPrimary tumor siteHigh unmet needUnmet medical needMonomethyl auristatin E.CPI therapyFatal AEsPrior chemotherapyPrior therapyRECIST v1.1Unconfirmed PRMetastatic settingPrimary endpoint
2017
793PD Phase 1 study of the PSMA-targeted small-molecule drug conjugate EC1169 in patients with metastatic castrate-resistant prostate cancer (mCRPC)
Morris M, Vogelzang N, Sartor O, Armour A, Groaning M, Messmann R, Robarts A, Petrylak D, Tolcher A, Gordon M, Babiker H. 793PD Phase 1 study of the PSMA-targeted small-molecule drug conjugate EC1169 in patients with metastatic castrate-resistant prostate cancer (mCRPC). Annals Of Oncology 2017, 28: v273. DOI: 10.1093/annonc/mdx370.010.Peer-Reviewed Original ResearchPhase 1 study of the PSMA-targeted small-molecule drug conjugate EC1169 in patients with metastatic castrate-resistant prostate cancer (mCRPC).
Morris M, Vogelzang N, Sartor O, Armour A, Groaning M, Robarts A, Petrylak D, Tolcher A, Gordon M, Babiker H. Phase 1 study of the PSMA-targeted small-molecule drug conjugate EC1169 in patients with metastatic castrate-resistant prostate cancer (mCRPC). Journal Of Clinical Oncology 2017, 35: 5038-5038. DOI: 10.1200/jco.2017.35.15_suppl.5038.Peer-Reviewed Original ResearchMetastatic castrate-resistant prostate cancerProstate-specific membrane antigenRadiographic progression-free survivalProstate cancerMedian radiographic progression-free survivalCastrate-resistant prostate cancerProgression-free survivalPhase 1 studySoft tissue diseasePatient selection toolPotential therapeutic targetAnti-tumor activityB ptsMost normal tissuesG3 thrombocytopeniaExpansion cohortPrimary endpointDose escalationMedian ageTissue diseaseRadiographic assessmentMedian numberDisease localizationDose reductionPart B
2016
731P Phase 1 study of the PSMA-targeted tubulysin small-molecule drug conjugate EC1169 in patients with metastatic castrate-resistant prostate cancer (mCRPC): Study update
Morris M, Vogelzang N, Sartor O, Armour A, Petrylak D, Tolcher A, Ejadi S, Babiker H. 731P Phase 1 study of the PSMA-targeted tubulysin small-molecule drug conjugate EC1169 in patients with metastatic castrate-resistant prostate cancer (mCRPC): Study update. Annals Of Oncology 2016, 27: vi249. DOI: 10.1093/annonc/mdw372.15.Peer-Reviewed Original ResearchPhase 1 study of the PSMA-targeted tubulysin small-molecule drug conjugate EC1169 in patients with metastatic castrate-resistant prostate cancer (mCRPC).
Morris M, Petrylak D, Sartor A, Vogelzang N, Groaning M, Ejadi S, Tolcher A, Babiker H. Phase 1 study of the PSMA-targeted tubulysin small-molecule drug conjugate EC1169 in patients with metastatic castrate-resistant prostate cancer (mCRPC). Journal Of Clinical Oncology 2016, 34: 2586-2586. DOI: 10.1200/jco.2016.34.15_suppl.2586.Peer-Reviewed Original Research
2015
A phase 2 study of prostate specific membrane antigen antibody drug conjugate (PSMA ADC) in patients (pts) with progressive metastatic castration-resistant prostate cancer (mCRPC) following abiraterone and/or enzalutamide (abi/enz).
Petrylak D, Vogelzang N, Chatta G, Fleming M, Smith D, Appleman L, Hussain A, Modiano M, Singh P, Tagawa S, Gore I, McClay E, Mega A, Sartor A, Somer B, Wadlow R, Shore N, Stambler N, DiPippo V, Israel R. A phase 2 study of prostate specific membrane antigen antibody drug conjugate (PSMA ADC) in patients (pts) with progressive metastatic castration-resistant prostate cancer (mCRPC) following abiraterone and/or enzalutamide (abi/enz). Journal Of Clinical Oncology 2015, 33: 144-144. DOI: 10.1200/jco.2015.33.7_suppl.144.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerCTC declineProgressive metastatic castration-resistant prostate cancerCastration-resistant prostate cancerAntitumor activityMeasurable target lesionsNeuroendocrine serum markersPhase 2 studyPhase 2 trialPhase 1 studyHigh PSMA expressionProstate cancer cellsPSMA-positive cellsRadiologic responseHuman IgG1 antibodyPSA declineRadiologic evidenceElectrolyte imbalanceSerum markersCTC countEfficacy responseTarget lesionsProstate cancerPSMA expressionEnz treatment