2023
First-in-class oral innate immune activator BXCL701 combined with pembrolizumab, in patients with metastatic castration-resistant prostate cancer (mCRPC) of small cell neuroendocrine (SCNC) variant: Randomized phase 2b trial.
Aggarwal R, Zhang J, Monk P, Zhu X, Costin D, Petrylak D, Borderies P, Deshpande R, Hafeez A, O'Neill V, Tagawa S. First-in-class oral innate immune activator BXCL701 combined with pembrolizumab, in patients with metastatic castration-resistant prostate cancer (mCRPC) of small cell neuroendocrine (SCNC) variant: Randomized phase 2b trial. Journal Of Clinical Oncology 2023, 41: tps5109-tps5109. DOI: 10.1200/jco.2023.41.16_suppl.tps5109.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerSerious adverse eventsPartial responsePrimary endpointPhase 2aRandomized Phase 2b TrialCastration-resistant prostate cancerOral small-molecule inhibitorPhase 2b trialPrime immune cellsRECIST 1.1 criteriaDisease control rateImmune checkpoint inhibitorsPhase 2 studyPlatinum-based chemotherapyDuration of responsePotential predictive biomarkersImmune effector cellsMeasurable diseaseNeuroendocrine variantPSA-PFSRECIST 1.1Safety populationCheckpoint inhibitorsData cutoffSafety 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 eventsFirst-in-class oral innate immune activator BXCL701 combined with pembrolizumab in patients with metastatic, castration-resistant prostate cancer (mCRPC) of small cell neuroendocrine (SCNC) phenotype: Phase 2a final results.
Aggarwal R, Zhang J, Zhu X, Monk P, Jones R, Linch M, Costin D, De Bono J, Karsh L, Petrylak D, Borderies P, Deshpande R, Hafeez A, O'Neill V, Tagawa S. First-in-class oral innate immune activator BXCL701 combined with pembrolizumab in patients with metastatic, castration-resistant prostate cancer (mCRPC) of small cell neuroendocrine (SCNC) phenotype: Phase 2a final results. Journal Of Clinical Oncology 2023, 41: 176-176. DOI: 10.1200/jco.2023.41.6_suppl.176.Peer-Reviewed Original ResearchEvaluable patientsMedian durationDay 1Castration-resistant prostate cancerOral small-molecule inhibitorEncouraging anti-tumor activityImmune-related AEPrime immune cellsAcceptable safety profilePhase 2 studyDurability of responsePlatinum-based chemotherapyImmune effector cellsStandard of careAnti-tumor activityComposite respondersRECIST respondersBID dosingCheckpoint inhibitorsMCRPC patientsPrimary endpointRECIST 1.1Acceptable tolerabilityAdverse eventsCytotoxic chemotherapyUpdated outcomes in TROPHY-U-01 cohort 1, a phase 2 study of sacituzumab govitecan (SG) in patients (pts) with metastatic urothelial cancer (mUC) that progressed after platinum (PT)-based chemotherapy and a checkpoint inhibitor (CPI).
Tagawa S, Balar A, Petrylak D, Rezazadeh A, Loriot Y, Flechon A, Jain R, Agarwal N, Bupathi M, Barthelemy P, Beuzeboc P, Palmbos P, Kyriakopoulos C, Pouessel D, Sternberg C, Tonelli J, Sierecki M, Zhou H, Grivas P. Updated outcomes in TROPHY-U-01 cohort 1, a phase 2 study of sacituzumab govitecan (SG) in patients (pts) with metastatic urothelial cancer (mUC) that progressed after platinum (PT)-based chemotherapy and a checkpoint inhibitor (CPI). Journal Of Clinical Oncology 2023, 41: 526-526. DOI: 10.1200/jco.2023.41.6_suppl.526.Peer-Reviewed Original ResearchMetastatic urothelial cancerTreatment-related adverse eventsObjective response rateProgression-free survivalDuration of responseClinical benefit ratePhase 2 studyCheckpoint inhibitorsSacituzumab govitecanOverall survivalPrior therapyCentral reviewResponse rateAnti-Trop-2 antibodyAccelerated FDA approvalECOG PS 0Last prior therapyTreatment-related deathsKey secondary endpointNew safety signalsFebrile neutropeniaOS ratesData cutoffPrimary endpointRECIST 1.1Pembrolizumab plus docetaxel for patients with metastatic castration-resistant prostate cancer (mCRPC): Randomized, double-blind, phase 3 KEYNOTE-921 study.
Petrylak D, Ratta R, Matsubara N, Korbenfeld E, Gafanov R, Mourey L, Todenhöfer T, Gurney H, Kramer G, Bergman A, Zalewski P, De Santis M, Armstrong A, Gerritsen W, Pachynski R, Byun S, Li X, Schloss C, Poehlein C, Fizazi K. Pembrolizumab plus docetaxel for patients with metastatic castration-resistant prostate cancer (mCRPC): Randomized, double-blind, phase 3 KEYNOTE-921 study. Journal Of Clinical Oncology 2023, 41: 19-19. DOI: 10.1200/jco.2023.41.6_suppl.19.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerNext-generation hormonal agentsDual primary endpointsTreatment-related AEsCycles of docetaxelPrimary endpointSecondary endpointsDocetaxel armRadiographic progression-free survivalCastration-resistant prostate cancerBlinded independent central reviewCycles of placeboData cutoff dateSafety of pembrolizumabSubsequent anticancer therapyTreatment-related deathsAndrogen deprivation therapyECOG performance statusKey secondary endpointProgression-free survivalIndependent central reviewEligible ptsDeprivation therapyRECIST 1.1Baseline characteristics
2022
BXCL701: First-in-class oral activator of systemic innate immunity combined with pembrolizumab, in patients with metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma phenotype—Phase 2a results.
Zhang J, Aggarwal R, Tagawa S, Linch M, Petrylak D, Costin D, De Bono J, Jones R, Karsh L, Zhu X, Borderies P, Deshpande R, O'Neill V, Monk P. BXCL701: First-in-class oral activator of systemic innate immunity combined with pembrolizumab, in patients with metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma phenotype—Phase 2a results. Journal Of Clinical Oncology 2022, 40: 125-125. DOI: 10.1200/jco.2022.40.6_suppl.125.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerAnti-tumor activityEvaluable patientsTaxane chemotherapyPrior linesAndrogen receptorProstate cancerAdenocarcinoma cohortCastration-resistant prostate cancerOral small-molecule inhibitorEncouraging anti-tumor activityBone-only diseaseComposite response rateImmune-related AEPhase 1b/2 studyPrime immune cellsSystemic innate immunityDisease control rateAcceptable safety profileMost prostate cancersAndrogen deprivation treatmentImmune effector cellsCTC conversionMeasurable diseaseRECIST 1.1BXCL701: First-in-class oral activator of systemic innate immunity combined with pembrolizumab, in patients with metastatic castration-resistant prostate cancer (mCRPC) of small-cell neuroendocrine carcinoma (SCNC) phenotype—Phase 2a interim results.
Tagawa S, Zhang J, Monk P, Zhu X, Jones R, Linch M, Costin D, De Bono J, Karsh L, Petrylak D, Borderies P, Deshpande R, O'Neill V, Aggarwal R. BXCL701: First-in-class oral activator of systemic innate immunity combined with pembrolizumab, in patients with metastatic castration-resistant prostate cancer (mCRPC) of small-cell neuroendocrine carcinoma (SCNC) phenotype—Phase 2a interim results. Journal Of Clinical Oncology 2022, 40: 126-126. DOI: 10.1200/jco.2022.40.6_suppl.126.Peer-Reviewed Original ResearchSmall cell neuroendocrine carcinomaMetastatic castration-resistant prostate cancerEvaluable patientsAnti-tumor activityPrior linesCastration-resistant prostate cancerOral small-molecule inhibitorEncouraging anti-tumor activityBone-only diseaseComposite response rateImmune-related AEPhase 1b/2 studyPrime immune cellsSystemic innate immunityAcceptable safety profileImmune effector cellsStandard of careInterim resultsStage 1Prior chemotherapyRECIST 1.1Unconfirmed PRBID dosingCheckpoint inhibitorsMCRPC patients
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 eventsEV-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 dosePhase I study of AMG 509, a STEAP1 x CD3 T-cell recruiting XmAb 2+1 immune therapy, in patients with metastatic castration-resistant prostate cancer (mCRPC).
Kelly W, Pook D, Appleman L, Waterhouse D, Horvath L, Edenfield W, Matsubara N, Danila D, Aggarwal R, Petrylak D, Sartor A, Sumey C, Adra N, Armstrong A, Cheng F, Stieglmaier J, Kouros-Mehr H, Dorff T. Phase I study of AMG 509, a STEAP1 x CD3 T-cell recruiting XmAb 2+1 immune therapy, in patients with metastatic castration-resistant prostate cancer (mCRPC). Journal Of Clinical Oncology 2021, 39: tps183-tps183. DOI: 10.1200/jco.2021.39.6_suppl.tps183.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerFirst doseImmune therapyProstate cancerECOG performance status 0Prostate-specific antigen (PSA) responseCastration-resistant prostate cancerT cell-mediated lysisDose-expansion phasePerformance status 0Phase 2 doseObjective tumor responseT effector cellsASCO Annual MeetingTotal serum testosteroneLogistic regression modelsCell surface antigensTransmembrane epithelial antigenTumor cell responseCNS metastasisLeptomeningeal diseaseRECIST 1.1Status 0Taxane regimensHormonal therapy
2020
Phase I study of AMG 509, a STEAP1 x CD3 T cell-recruiting XmAb 2+1 immune therapy, in patients with metastatic castration-resistant prostate cancer (mCRPC).
Kelly W, Danila D, Edenfield W, Aggarwal R, Petrylak D, Sartor A, Sumey C, Dorff T, Yu E, Adra N, Waterhouse D, Armstrong A, Horvath L, Pook D, Appleman L, Lau A, Salvati M, Kouros-Mehr H. Phase I study of AMG 509, a STEAP1 x CD3 T cell-recruiting XmAb 2+1 immune therapy, in patients with metastatic castration-resistant prostate cancer (mCRPC). Journal Of Clinical Oncology 2020, 38: tps5589-tps5589. DOI: 10.1200/jco.2020.38.15_suppl.tps5589.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerFirst doseImmune therapyProstate cancerECOG performance status 0Prostate-specific antigen (PSA) responseCastration-resistant prostate cancerT cell-mediated lysisPhase IDose-expansion phasePerformance status 0Objective tumor responsePhase II doseT effector cellsTotal serum testosteroneLogistic regression modelsCell surface antigensTransmembrane epithelial antigenTumor cell responseCNS metastasisLeptomeningeal diseaseRECIST 1.1Status 0Taxane regimensHormonal therapy
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 neuropathySacituzumab govitecan (IMMU-132) in patients with previously treated metastatic urothelial cancer (mUC): Results from a phase I/II study.
Tagawa S, Faltas B, Lam E, Saylor P, Bardia A, Hajdenberg J, Morgans A, Lim E, Kalinsky K, Simpson P, Galsky M, Goswam T, Wegener W, Petrylak D. Sacituzumab govitecan (IMMU-132) in patients with previously treated metastatic urothelial cancer (mUC): Results from a phase I/II study. Journal Of Clinical Oncology 2019, 37: 354-354. DOI: 10.1200/jco.2019.37.7_suppl.354.Peer-Reviewed Original ResearchMetastatic urothelial cancerObjective response rateProgression-free survivalDuration of responseSacituzumab govitecanOverall survivalPhase I/II studyImmune checkpoint inhibitor therapyMedian DORMedian progression-free survivalNeutropenia/neutrophil countNovel antibody-drug conjugateClinical benefit rateEpithelial cell surface antigenPrior treatment linesCheckpoint inhibitor therapyAdvanced solid tumorsCT/MRI scansPhase 2 trialLimited treatment optionsCell surface antigensAntibody-drug conjugatesAdvanced UCFebrile neutropeniaRECIST 1.1TROPHY-u-01: A phase II open-label study of sacituzumab govitecan (IMMU-132) in patients with advanced urothelial cancer after progression on platinum-based chemotherapy and/or anti-PD-1/PD-L1 checkpoint inhibitor therapy.
Tagawa S, Petrylak D, Grivas P, Agarwal N, Sternberg C, Siemon-Hryczyk P, Goswam T, Loriot Y. TROPHY-u-01: A phase II open-label study of sacituzumab govitecan (IMMU-132) in patients with advanced urothelial cancer after progression on platinum-based chemotherapy and/or anti-PD-1/PD-L1 checkpoint inhibitor therapy. Journal Of Clinical Oncology 2019, 37: tps495-tps495. DOI: 10.1200/jco.2019.37.7_suppl.tps495.Peer-Reviewed Original ResearchObjective response rateMetastatic urothelial cancerPlatinum-based chemotherapyCheckpoint inhibitor therapyPhase 2 trialSacituzumab govitecanAdverse eventsInhibitor therapyUrothelial cancerPhase II open-label studyTrop-2Median progression-free survivalAdvanced urothelial cancerEpithelial cell surface antigenMedian overall survivalOpen-label studySafety/tolerabilityProgression-free survivalSingle-arm trialCell surface antigensAdvanced UCEvaluable ptsPrior therapyRECIST 1.1Overall survival
2015
Phase 1/2 trial of cabazitaxel with abiraterone acetate in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel and abiraterone acetate: Phase 2 results.
Mateo J, Fizazi K, Pezaro C, Loriot Y, Mehra N, Albiges L, Bianchini D, Varga A, Ryan C, Petrylak D, Shen L, Zhang J, Attard G, De Bono J, Massard C. Phase 1/2 trial of cabazitaxel with abiraterone acetate in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel and abiraterone acetate: Phase 2 results. Journal Of Clinical Oncology 2015, 33: 268-268. DOI: 10.1200/jco.2015.33.7_suppl.268.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerPhase 2 partProgression-free survivalAbiraterone acetateAdverse eventsPrimary endpointTreatment-emergent adverse eventsCastration-resistant prostate cancerECOG PS 0Median PSA-PFSPSA response rateAntitumor activityOpen-label trialDuration of responseCombination of abirateroneMeasurable diseasePSA-PFSRECIST 1.1Secondary endpointsDose intensityOverall survivalPartial responsePS 0PSA responseMedian time
2013
A phase I/II study of safety and efficacy of orteronel (TAK-700), an oral, investigational, nonsteroidal 17,20-lyase inhibitor, with docetaxel and prednisone (DP) in metastatic castration-resistant prostate cancer (mCRPC): Updated phase II results.
Petrylak D, Gandhi J, Clark W, Heath E, Lin J, Oh W, Agus D, Carthon B, Moran S, Kong N, Suri A, Bargfrede M, Liu G. A phase I/II study of safety and efficacy of orteronel (TAK-700), an oral, investigational, nonsteroidal 17,20-lyase inhibitor, with docetaxel and prednisone (DP) in metastatic castration-resistant prostate cancer (mCRPC): Updated phase II results. Journal Of Clinical Oncology 2013, 31: 59-59. DOI: 10.1200/jco.2013.31.6_suppl.59.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerPSA responseMedian timePhase I/II studyCastration-resistant prostate cancerDrug-related SAEsECOG PS 0/1Good PSA responseProgression of PsAPhase 1/2 studyPartial tumor responsePhase II resultsBlood alkaline phosphataseCastrate menPS 0/1Median PSAPrior chemotherapyPSA declinePSA progressionRadiologic progressionRECIST 1.1Data cutoffII studyRadiographic diseaseSerum PSA
2012
918P Phase 2 Results from a Phase 1/2 Study of Tak-700 (ORTERONEL), An Oral, Investigational, Nonsteroidal 17,20-Lyase Inhibitor, with Docetaxel and Prednisone (DP) in Metastatic Castration-Resistant Prostate Cancer (MCRPC)
Petrylak D, Gandhi J, Clark W, Heath E, Lin J, Oh W, Agus D, Carthon B, Moran S, Liu G. 918P Phase 2 Results from a Phase 1/2 Study of Tak-700 (ORTERONEL), An Oral, Investigational, Nonsteroidal 17,20-Lyase Inhibitor, with Docetaxel and Prednisone (DP) in Metastatic Castration-Resistant Prostate Cancer (MCRPC). Annals Of Oncology 2012, 23: ix302-ix303. DOI: 10.1016/s0923-7534(20)33476-1.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerPhase 1/2 studyTAK-700Febrile neutropeniaMedian timeCastration-resistant prostate cancerDrug-related SAEsECOG PS 0/1Good PSA responseProgression of PsAPSA response rateTreatment-related AEsPartial tumor responseLyase inhibitorMillennium PharmaceuticalsGlaxo Smith KlineCastrate menEvaluable populationPrior chemotherapyPS 0/1PSA declinePSA progressionRadiologic progressionRECIST 1.1Data cutoff