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
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 trial
2022
TROPHY-U-01 cohort 4: Sacituzumab govitecan (SG) in combination with cisplatin (Cis) in platinum (PLT)-naïve patients (pts) with metastatic urothelial cancer (mUC).
Tagawa S, Grivas P, Petrylak D, Sternberg C, Swami U, Bhatia A, Pichardo C, Goswami T, Loriot Y. TROPHY-U-01 cohort 4: Sacituzumab govitecan (SG) in combination with cisplatin (Cis) in platinum (PLT)-naïve patients (pts) with metastatic urothelial cancer (mUC). Journal Of Clinical Oncology 2022, 40: tps581-tps581. DOI: 10.1200/jco.2022.40.6_suppl.tps581.Peer-Reviewed Original ResearchMetastatic urothelial cancerBlinded independent central reviewObjective response rateSacituzumab govitecanOverall survivalDay 1Antibody-drug conjugatesCohort 4Eastern Cooperative Oncology Group performance status 0Prophylactic granulocyte colony-stimulating factorActive interstitial lung diseaseAntigen 2 antibodiesClinical benefit ratePerformance status 0Phase 2 doseStudy drug initiationMedian overall survivalProgression-free survivalPhase 2 trialDose-limiting toxicityInterstitial lung diseaseDuration of responseEfficacy/safetyGranulocyte colony-stimulating factorIndependent central review
2020
Safety and clinical activity of atezolizumab (atezo) + radium-223 dichloride (r-223) in 2L metastatic castration-resistant prostate cancer (mCRPC): Results from a phase Ib clinical trial.
Morris M, Fong L, Petrylak D, Sartor A, Higano C, Pagliaro L, Alva A, Appleman L, Tan W, Vaishampayan U, Porcu R, Tayama D, Kadel E, Yuen K, Datye A, Armstrong A. Safety and clinical activity of atezolizumab (atezo) + radium-223 dichloride (r-223) in 2L metastatic castration-resistant prostate cancer (mCRPC): Results from a phase Ib clinical trial. Journal Of Clinical Oncology 2020, 38: 5565-5565. DOI: 10.1200/jco.2020.38.15_suppl.5565.Peer-Reviewed Original ResearchMetastatic castration-resistant prostate cancerPSA response ratePSA progressionDosing schedulesPD-L1Clinical benefitResponse ratePD-1/PD-L1Castration-resistant prostate cancerPhase Ib clinical trialPhase 1b studyPhase Ib studyTumor-directed radiationAnti-tumor immunityDose-limiting toxicityRadium-223 dichlorideLimited treatment optionsMechanism of actionEvaluable ptsRadiographic PFSMCRPC patientsMedian OSBaseline characteristicsEvaluable dataUnacceptable toxicity
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 levels
2014
Evaluating the safety of abiraterone acetate (AA) and docetaxel (D) administered in combination in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC).
Tagawa S, Nanus D, Posadas E, Petrylak D, Bruce J, Lim E, Peng W, Maul R, Gonzalez M, Tran N. Evaluating the safety of abiraterone acetate (AA) and docetaxel (D) administered in combination in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC). Journal Of Clinical Oncology 2014, 32: 205-205. DOI: 10.1200/jco.2014.32.4_suppl.205.Peer-Reviewed Original ResearchDose-limiting toxicityMetastatic castration-resistant prostate cancerAbiraterone acetateExperienced dose-limiting toxicityProstate-specific antigen (PSA) declineCastration-resistant prostate cancerPhase Ib studyMaximum plasma concentrationConcentration-time curveIntolerable toxicityPSA progressionMedian timeSystemic exposurePlasma concentrationsProstate cancerIb studyPharmacokinetic parametersFurther evaluationWk 2Wk 7CohortToxicityComplementary mechanismsProportion of PtSafety