2024
ARV-766, a proteolysis targeting chimera (PROTAC) androgen receptor (AR) degrader, in metastatic castration-resistant prostate cancer (mCRPC): Initial results of a phase 1/2 study.
Petrylak D, McKean M, Lang J, Gao X, Dreicer R, Geynisman D, Stewart T, Gandhi M, Appleman L, Dorff T, Chatta G, Tutrone R, De La Cerda J, Berghorn E, Gong J, Yu T, Dominy E, Chan E, Shore N. ARV-766, a proteolysis targeting chimera (PROTAC) androgen receptor (AR) degrader, in metastatic castration-resistant prostate cancer (mCRPC): Initial results of a phase 1/2 study. Journal Of Clinical Oncology 2024, 42: 5011-5011. DOI: 10.1200/jco.2024.42.16_suppl.5011.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerTreatment-related adverse eventsAR-LBD mutationsPhase 1/2 studyClinical activityProstate cancerAndrogen receptorAdverse eventsMetastatic castration-resistant prostate cancer treatmentProgressive metastatic castration-resistant prostate cancerPhase 1 dose-escalation portionDisease progressionTreatment-emergent adverse eventsCastration-resistant prostate cancerResistant to available therapiesAssociated with poor outcomesDose-limiting toxicityAndrogen deprivation therapyAdvanced prostate cancerIncreased blood creatinineWild-type ARSubgroup of patientsDose-dependent increaseDeprivation therapyPretreated patients
2022
Phase 1/2 study of ARV-110, an androgen receptor (AR) PROTAC degrader, in metastatic castration-resistant prostate cancer (mCRPC).
Gao X, Burris H, Vuky J, Dreicer R, Sartor A, Sternberg C, Percent I, Hussain M, Kalebasty A, Shen J, Heath E, Abesada-Terk G, Gandhi S, McKean M, Lu H, Berghorn E, Gedrich R, Chirnomas S, Vogelzang N, Petrylak D. Phase 1/2 study of ARV-110, an androgen receptor (AR) PROTAC degrader, in metastatic castration-resistant prostate cancer (mCRPC). Journal Of Clinical Oncology 2022, 40: 17-17. DOI: 10.1200/jco.2022.40.6_suppl.017.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerNovel hormonal agentsProstate-specific antigenClinical activityBetter prostate-specific antigenOngoing phase 1/2 studyCastration-resistant prostate cancerBiomarker-defined subgroupsPhase 2 dosePhase 1/2 studyWild-type ARFourth subgroupPhase 1AR alterationsRECIST responseSpecific molecular profilePrior therapyAdverse eventsAR-V7Tumor shrinkageHormonal agentsTreatment optionsClinical historyDisease progressionProstate cancerImpact of primary tumor location on efficacy and safety of pembrolizumab (pembro) in patients (pts) with locally advanced or metastatic urothelial carcinoma (UC) enrolled in the phase 2 KEYNOTE-052 and phase 3 KEYNOTE-045 trials.
O'Donnell P, Balar A, Castellano D, De Wit R, Vaughn D, Powles T, Vuky J, Lee J, Fradet Y, Bellmunt J, Fong L, Petrylak D, Gerritsen W, Quinn D, Culine S, Bajorin D, Xu J, Imai K, Moreno B, Grivas P. Impact of primary tumor location on efficacy and safety of pembrolizumab (pembro) in patients (pts) with locally advanced or metastatic urothelial carcinoma (UC) enrolled in the phase 2 KEYNOTE-052 and phase 3 KEYNOTE-045 trials. Journal Of Clinical Oncology 2022, 40: 516-516. DOI: 10.1200/jco.2022.40.6_suppl.516.Peer-Reviewed Original ResearchMetastatic urothelial carcinomaPrimary tumor locationKEYNOTE-045KEYNOTE-052Urothelial carcinomaTumor locationRECIST v1.1Primary tumorSafety of pembrolizumabSimilar clinical activityWithdrawal of consentMeasurable diseaseData cutoffManageable safetyUnacceptable toxicitySystemic therapyPD-L1Positive tumorsRenal pelvisDisease progressionPembroSimilar efficacyClinical activityGrade 3UT group
2020
BT8009-100 phase I/II study of the safety, pharmacokinetics, & preliminary clinical activity of BT8009 in patients with Nectin-4 expressing advanced malignancies
Mckean M, Bendell J, Petrylak D, Powles T, Sonpavde G, Dickson A, Dosunmu L, Hennessy M, Jeffrey P, Rigby M, West T. BT8009-100 phase I/II study of the safety, pharmacokinetics, & preliminary clinical activity of BT8009 in patients with Nectin-4 expressing advanced malignancies. Annals Of Oncology 2020, 31: s500-s501. DOI: 10.1016/j.annonc.2020.08.713.Peer-Reviewed Original ResearchRelationship between hyperphosphatemia with infigratinib (BGJ398) and efficacy in FGFR3 -altered advanced/metastatic urothelial carcinoma (aUC).
Lyou Y, Grivas P, Rosenberg J, Hoffman-Censits J, Quinn D, Petrylak D, Galsky M, Vaishampayan U, De Giorgi U, Gupta S, Burris H, Rearden J, Ye Y, Wang H, Moran S, Daneshmand S, Bajorin D, Pal S. Relationship between hyperphosphatemia with infigratinib (BGJ398) and efficacy in FGFR3 -altered advanced/metastatic urothelial carcinoma (aUC). Journal Of Clinical Oncology 2020, 38: 576-576. DOI: 10.1200/jco.2020.38.6_suppl.576.Peer-Reviewed Original ResearchDisease control rateOverall response rateTreatment lengthFGFR inhibitorsPrior platinum-based chemotherapyClass effectMedian treatment lengthRECIST 1.0 criteriaCommon adverse eventsMetastatic urothelial carcinomaSignificant clinical activityPlatinum-based chemotherapyPhosphate binder sevelamerMutations/fusionsEligible patientsEfficacy outcomesUnacceptable toxicityAdverse eventsFGFR3 alterationsEfficacy findingsUrothelial carcinomaControl ratePharmacodynamic biomarkersDisease progressionClinical activity
2014
Inhibition of PD-L1 by MPDL3280A and clinical activity in pts with metastatic urothelial bladder cancer (UBC).
Powles T, Vogelzang N, Fine G, Eder J, Braiteh F, Loriot Y, Cruz Zambrano C, Bellmunt J, Burris H, Teng S, Shen X, Koeppen H, Hegde P, Chen D, Petrylak D. Inhibition of PD-L1 by MPDL3280A and clinical activity in pts with metastatic urothelial bladder cancer (UBC). Journal Of Clinical Oncology 2014, 32: 5011-5011. DOI: 10.1200/jco.2014.32.15_suppl.5011.Peer-Reviewed Original Research
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 schedule