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 trialFirst-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 therapyA phase 2 expansion study of ARV-766, a PROTAC androgen receptor (AR) degrader, in metastatic castration-resistant prostate cancer (mCRPC).
Petrylak D, Stewart T, Gao X, Berghorn E, Lu H, Chan E, Gedrich R, Lang J, McKean M. A phase 2 expansion study of ARV-766, a PROTAC androgen receptor (AR) degrader, in metastatic castration-resistant prostate cancer (mCRPC). Journal Of Clinical Oncology 2023, 41: tps290-tps290. DOI: 10.1200/jco.2023.41.6_suppl.tps290.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerNovel hormonal agentsCohort expansionDisease progressionEastern Cooperative Oncology Group performance status scoreOngoing androgen deprivation therapyProstate-specific antigen (PSA) declineCastration-resistant prostate cancerGonadotropin-releasing hormone analogueCohort expansion studyAndrogen deprivation therapyPerformance status scoreOverall response ratePhase 1 portionWild-type ARDeprivation therapyPrior chemotherapyCurative optionDose escalationAvailable therapiesHormonal agentsStatus scoreCurrent therapiesLigand-binding domainClinical trials
2020
First-in-human phase I study of ARV-110, an androgen receptor (AR) PROTAC degrader in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) following enzalutamide (ENZ) and/or abiraterone (ABI).
Petrylak D, Gao X, Vogelzang N, Garfield M, Taylor I, Dougan Moore M, Peck R, Burris H. First-in-human phase I study of ARV-110, an androgen receptor (AR) PROTAC degrader in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) following enzalutamide (ENZ) and/or abiraterone (ABI). Journal Of Clinical Oncology 2020, 38: 3500-3500. DOI: 10.1200/jco.2020.38.15_suppl.3500.Peer-Reviewed Original ResearchMetastatic castrate-resistant prostate cancerAST/ALTAdverse eventsPSA responseAnti-tumor activityPrior therapyAST/ALT elevationElevated AST/ALTCastrate-resistant prostate cancerProstate cancer xenograft modelPreclinical anti-tumor activityPhase 2 doseRECIST partial responseAcceptable safety profileAcute renal failureHuman phase ICancer xenograft modelPrior chemotherapyALT elevationData cutoffRenal failurePartial responseDose escalationRadium-223Enz resistanceMEDI3726, 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
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
2012
Phase I results from a phase I/II study of 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, Kucuk O, Moran S, Wang J, Bargfrede M, Liu G. Phase I results from a phase I/II study of orteronel, an oral, investigational, nonsteroidal 17,20-lyase inhibitor, with docetaxel and prednisone (DP) in metastatic castration-resistant prostate cancer (mCRPC). Journal Of Clinical Oncology 2012, 30: 4656-4656. DOI: 10.1200/jco.2012.30.15_suppl.4656.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerSerious AEsFebrile neutropeniaCohort 1Phase I/II studyCastration-resistant prostate cancerCommon serious AEsECOG PS 0/1Median age 68Median PSA declinePhase 1/2 studyPhase II portionLyase inhibitorCastrate menPS 0/1Measurable diseaseMedian PSAPrior chemotherapyPSA declineII studyInfusion reactionsNeutrophil countStandard chemotherapyDose escalationWBC countProstate-specific membrane antigen antibody drug conjugate (PSMA ADC): A phase I trial in metastatic castration-resistant prostate cancer (mCRPC) previously treated with a taxane.
Mega A, Petrylak D, Kantoff P, Stephenson J, Vogelzang N, Dreicer R, Shore N, Stambler N, Carpenito J, D'Ambrosio P, 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 2012, 30: 4662-4662. DOI: 10.1200/jco.2012.30.15_suppl.4662.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerMonomethyl auristatin EHighest dose levelFree MMAEProstate cancer cellsDose levelsAdverse eventsProgressive metastatic castration-resistant prostate cancerPhase 1 dose-escalation studyCastration-resistant prostate cancerTumor cellsHigh-dose cohortTaxane-containing chemotherapyAntitumor activityCommon laboratory abnormalitiesDose-escalation studyLiver function testsPhase I trialCancer cellsClinical disease progressionDose cohortsECOG statusEscalation studyLaboratory abnormalitiesDose escalation
2011
Preliminary Results of An Ongoing Phase I Trial of Oral Belinostat a Novel Histone Deacetylase Inhibitor in Patients with Lymphoid Malignancies,
Zain J, Foss F, Diefenbach C, Petrylak D, Narwal A, Neylon E, Knoblauch P, O'Connor O. Preliminary Results of An Ongoing Phase I Trial of Oral Belinostat a Novel Histone Deacetylase Inhibitor in Patients with Lymphoid Malignancies,. Blood 2011, 118: 3710. DOI: 10.1182/blood.v118.21.3710.3710.Peer-Reviewed Original ResearchHistone deacetylase inhibitorsTumor shrinkageSolid tumorsDeacetylase inhibitorsIntra-patient dose escalationOngoing phase I trialClass I/II histone deacetylase inhibitorEarly tumor shrinkageGrade 3 diarrheaMedian age 48Frequent adverse eventsNovel histone deacetylase inhibitorPhase I trialHighest dose levelMantle cell lymphomaAnorexia/Dose cohortsEvaluable diseaseQ3w scheduleStable diseaseAdverse eventsDaily doseDose escalationI trialNHL patients
2009
Final results of a phase I study of oral belinostat (PXD101) in patients with solid tumors
Kelly W, DeBono J, Blumenschein G, Lassen U, Zain J, O'Connor O, Foss F, Tjornelund J, Fagerberg J, Petrylak D. Final results of a phase I study of oral belinostat (PXD101) in patients with solid tumors. Journal Of Clinical Oncology 2009, 27: 3531-3531. DOI: 10.1200/jco.2009.27.15_suppl.3531.Peer-Reviewed Original ResearchAdverse eventsFrequent related adverse eventsRelated adverse eventsMedian age 60Histone deacetylase inhibitorsMajor cancer typesMultiple tumor typesDaily x5Overall tolerabilityDose escalationQTc prolongationSafety profilePreclinical activityClinical activitySerial ECGsDay 1Age 60Solid tumorsTumor typesDeacetylase inhibitorsCohort 2aFurther evaluationPharmacokineticsCancer typesMultiple scheduleFinal results of a phase I study of oral belinostat (PXD101) in patients with lymphoma
Zain J, Foss F, Kelly W, DeBono J, Petrylak D, Narwal A, Neylon E, Blumenschein G, Lassen U, O'Connor O. Final results of a phase I study of oral belinostat (PXD101) in patients with lymphoma. Journal Of Clinical Oncology 2009, 27: 8580-8580. DOI: 10.1200/jco.2009.27.15_suppl.8580.Peer-Reviewed Original ResearchNon-Hodgkin lymphomaHodgkin's diseaseDose escalationTumor shrinkageSolid tumorsIntra-patient dose escalationRefractory non-Hodgkin lymphomaPhase IAcceptable organ functionEarly tumor shrinkageMedian age 51Frequent adverse eventsPossible dose escalationMantle cell lymphomaHistone deacetylase inhibitorsEvaluable diseaseLeg DVTPrior regimensQ3w scheduleStable diseaseAdverse eventsDaily doseSafety profileCohort C.Preclinical activity