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
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 response
2018
PSMA heterogeneity analysis in patients with metastatic castrate-resistant prostate cancer (mCRPC): Imaging versus CTCs.
Morris M, Vogelzang N, Sartor A, Armour A, Messmann R, Groaning M, Robarts A, Tolcher A, Gordon M, Babiker H, Kuo P, Kearney M, Jendrisak A, Wang Y, Landers M, Petrylak D. PSMA heterogeneity analysis in patients with metastatic castrate-resistant prostate cancer (mCRPC): Imaging versus CTCs. Journal Of Clinical Oncology 2018, 36: 272-272. DOI: 10.1200/jco.2018.36.6_suppl.272.Peer-Reviewed Original ResearchMetastatic castrate-resistant prostate cancerProstate-specific membrane antigenSPECT/CT scansHomologous recombination deficiency scoresPSMA expressionProstate cancerCT scanPre-treatment blood samplesDeficiency scoresCastrate-resistant prostate cancerBiomarker analysisSoft tissue lesionsSPECT/CTTherapeutic predictive valueDetectable CTCsNaïve patientsBone scanBad respondersClinical outcomesBaseline CTBone lesionsPositive lesionsBlood samplesTissue lesionsTherapeutic target
2017
A phase 1/1b multicenter, open-label, dose escalation and dose expansion study to evaluate the safety, pharmacokinetics, immunogenicity, and antitumor activity of MEDI3726 in patients with metastatic, castration-resistant prostate cancer who have received prior treatment with abiraterone or enzalutamide.
Fleming M, Cathomas R, Petrylak D, Wang J, Bander N, Zammarchi F, van Berkel P, Cho S, Elgeioushi N, Bothos J, Scheuber A, de Bono J. A phase 1/1b multicenter, open-label, dose escalation and dose expansion study to evaluate the safety, pharmacokinetics, immunogenicity, and antitumor activity of MEDI3726 in patients with metastatic, castration-resistant prostate cancer who have received prior treatment with abiraterone or enzalutamide. Journal Of Clinical Oncology 2017, 35: tps5088-tps5088. DOI: 10.1200/jco.2017.35.15_suppl.tps5088.Peer-Reviewed Original ResearchProstate-specific membrane antigenCastration-resistant prostate cancerDose-expansion studyAbiraterone acetateProstate cancerDose escalationAntitumor activityPrior treatmentTaxane-based chemotherapyDose-limiting toxicityFurther treatment optionsAnti-PSMA antibodyVivo antitumor activityTarget enrollmentTreatment optionsTherapeutic advancesPreclinical modelsPatientsMembrane antigenSecondary objectiveCancerMCRPCMulticenterTolerabilityExpression levelsPhase 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
2014
A phase II trial of prostate-specific membrane antigen antibody drug conjugate (PSMA ADC) in taxane-refractory metastatic castration-resistant prostate cancer (mCRPC).
Petrylak D, Smith D, Appleman L, Fleming M, Hussain A, Dreicer R, Sartor A, Shore N, Vogelzang N, Youssoufian H, Olson W, Stambler N, Huang K, Israel R. A phase II trial of prostate-specific membrane antigen antibody drug conjugate (PSMA ADC) in taxane-refractory metastatic castration-resistant prostate cancer (mCRPC). Journal Of Clinical Oncology 2014, 32: 83-83. DOI: 10.1200/jco.2014.32.4_suppl.83.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerProstate-specific membrane antigenProgressive metastatic castration-resistant prostate cancerProstate-specific antigenCastration-resistant prostate cancerMonomethyl auristatin EPhase II trialAdverse eventsII trialTumor responseProstate cancerECOG PS 0Significant adverse eventsAntibody drugsFree MMAEHigh PSMA expressionAnti-tumor activityProstate cancer cellsCTC declinePrior docetaxelPSA declinePS 0Peripheral neuropathyPSA reductionAntibody therapy
2013
Prostate-specific membrane antigen antibody drug conjugate (PSMA ADC): A phase I trial in metastatic castration-resistant prostate cancer (mCRPC) previously treated with a taxane.
Petrylak D, Kantoff P, Mega A, Vogelzang N, Stephenson J, Fleming M, Stambler N, Petrini M, Blattman S, Israel R. Prostate-specific membrane antigen antibody drug conjugate (PSMA ADC): A phase I trial in metastatic castration-resistant prostate cancer (mCRPC) previously treated with a taxane. Journal Of Clinical Oncology 2013, 31: 5018-5018. DOI: 10.1200/jco.2013.31.15_suppl.5018.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerProstate-specific membrane antigenProgressive metastatic castration-resistant prostate cancerMonomethyl auristatin ELiver function testsFree MMAEPhase 1 dose-escalation studyCastration-resistant prostate cancerTaxane-containing chemotherapyAntitumor activityDose-escalation studyPhase 2 trialPhase I trialCancer cellsProstate cancer cellsSpecific membrane antigenECOG statusLFT abnormalitiesPrior docetaxelAdverse eventsEscalation studyI trialPeripheral neuropathyAntibody therapyFunction testsProstate-specific membrane antigen antibody drug conjugate (PSMA ADC): A phase I trial in metastatic castration-resistant prostate cancer (mCRPC) previously treated with a taxane.
Petrylak D, Kantoff P, Mega A, Vogelzang N, Stephenson J, Fleming M, Stambler N, Petrini M, Huang K, Israel R. Prostate-specific membrane antigen antibody drug conjugate (PSMA ADC): A phase I trial in metastatic castration-resistant prostate cancer (mCRPC) previously treated with a taxane. Journal Of Clinical Oncology 2013, 31: 119-119. DOI: 10.1200/jco.2013.31.6_suppl.119.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerProstate-specific membrane antigenMonomethyl auristatin EFree MMAEProstate cancer cellsProgressive metastatic castration-resistant prostate cancerDose levelsPhase 1 dose-escalation studyLiver function test elevationsCastration-resistant prostate cancerTaxane-containing chemotherapyAntitumor activityDose-escalation studyPhase 2 trialPhase I trialCancer cellsClinical disease progressionHighest dose levelSpecific membrane antigenECOG statusLFT abnormalitiesPrior docetaxelAdverse eventsEscalation studyI trial
1996
Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy
Wright G, Grob B, Haley C, Grossman K, Newhall K, Petrylak D, Troyer J, Konchuba A, Schellhammer P, Moriarty R. Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy. Urology 1996, 48: 326-334. PMID: 8753752, DOI: 10.1016/s0090-4295(96)00184-7.Peer-Reviewed Original ResearchConceptsProstate-specific membrane antigenAndrogen deprivation therapyExpression of PSMAProstate cancerLNCaP cellsAndrogen deprivationMetastatic specimensMembrane antigenCombination androgen deprivation therapyProstate-specific antigen expressionTissue specimensAntigen-positive tumor cellsHormone-independent prostate cancerPost-treatment specimenAndrogen deprivation treatmentAbsence of androgenPresence of testosteroneExtent of stainingWestern blot analysisAndrogen treatmentPSA expressionMetastatic tissuesPSMA expressionAntigen expressionProstate carcinoma