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MP82-09 PROSTATE SPECIFIC MEMBRANE ANTIGEN ANTIBODY DRUG CONJUGATE (PSMA ADC) IN PATIENTS (PTS) WITH PROGRESSIVE METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (MCRPC) FOLLOWING ABIRATERONE AND/OR ENZALUTAMIDE (ABI/ENZ): RESULTS FROM A PHASE 2 STUDY

2015; Lippincott Williams & Wilkins; Volume: 193; Issue: 4S Linguagem: Inglês

10.1016/j.juro.2015.02.528

1527-3792

Daniel P. Petrylak, Nicholas J. Vogelzang, Kamal Chatta, Mark T. Fleming, David C. Smith, Leonard J. Appleman, Arif Hussain, Manuel Modiano, Parminder Singh, Scott T. Tagawa, Ira Gore, Ed McClay, Anthony Mega, Oliver Sartor, Brad Somer, Raymond Wadlow, Neal D. Shore, Nancy Stambler, Vincent A. DiPippo, Robert J. Israel,

Radiopharmaceutical Chemistry and Applications

You have accessJournal of UrologyProstate Cancer: Advanced II1 Apr 2015MP82-09 PROSTATE SPECIFIC MEMBRANE ANTIGEN ANTIBODY DRUG CONJUGATE (PSMA ADC) IN PATIENTS (PTS) WITH PROGRESSIVE METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (MCRPC) FOLLOWING ABIRATERONE AND/OR ENZALUTAMIDE (ABI/ENZ): RESULTS FROM A PHASE 2 STUDY Daniel Petrylak, Nicholas Vogelzang, Kamal Chatta, Mark Fleming, David Smith, Leonard Appleman, Arif Hussain, Manuel Modiano, Parminder Singh, Scott Tagawa, Ira Gore, Ed McClay, Anthony Mega, Oliver Sartor, Brad Somer, Raymond Wadlow, Neal Shore, Nancy Stambler, Vincent DiPippo, and Robert Israel Daniel PetrylakDaniel Petrylak , Nicholas VogelzangNicholas Vogelzang , Kamal ChattaKamal Chatta , Mark FlemingMark Fleming , David SmithDavid Smith , Leonard ApplemanLeonard Appleman , Arif HussainArif Hussain , Manuel ModianoManuel Modiano , Parminder SinghParminder Singh , Scott TagawaScott Tagawa , Ira GoreIra Gore , Ed McClayEd McClay , Anthony MegaAnthony Mega , Oliver SartorOliver Sartor , Brad SomerBrad Somer , Raymond WadlowRaymond Wadlow , Neal ShoreNeal Shore , Nancy StamblerNancy Stambler , Vincent DiPippoVincent DiPippo , and Robert IsraelRobert Israel View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.528AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES PSMA is a validated target that is overexpressed selectively on prostate cancer cells. PSMA ADC is a fully human IgG1 antibody conjugated to the microtubule disrupting agent monomethyl auristatin E (MMAE) which binds to PSMA-positive cells, inducing cytotoxicity. A phase 1 study showed activity and tolerability at doses from 1.8-2.5 mg/kg. To further assess PSMA ADC, we have enrolled in a phase 2 trial 119 mCRPC pts who progressed following abi/enz. METHODS mCRPC pts (83 taxane experienced (TE) and 36 chemo-naive (CN)) were administered PSMA ADC 2.5 or 2.3 mg/kg IV Q3 wk for up to 8 cycles. 95% of pts received prior abi/enz treatment. Safety, antitumor activity (including prostate specific antigen (PSA), circulating tumor cells (CTCs), and tumor imaging) and exploratory biomarkers were assessed. RESULTS In all treated pts, PSA declines of ≥30% and ≥50% were 30% and 14%, respectively (n=113); CTC counts showed a decline of ≥50% in 78% of pts and conversion from ≥5 to <5 cells/7.5 ml blood in 47% (n=77) at any time during the study. For 2.3 mg/kg pts (n=82), corresponding PSA declines were 35% and 17%; CTC declines of ≥50% were seen in 81% and conversions in 46% (n=54). For CN pts, PSA declines of ≥30% and ≥50% were 31% and 20% (n=35) vs. 29% and 12% in TE pts (n=78). CTC declines of ≥50% were seen in 89% and conversion in 53% (n=19; CN) vs. 74% and 45% (n=58; TE). Radiologic responses (RECIST) in 31 pts with measurable target lesions were: partial response, 27% CN; 5% TE; stable disease, 55% CN; 65% TE; progressive disease, 18% CN; 30% TE. Efficacy responses were associated with: low neuroendocrine serum markers (low chromogranin A, low neuron specifc enolase, and high PSA), high PSMA expression (CTCs or tumor tissue). The most common treatment-related adverse events (AEs) ≥CTCAE grade 3 were neutropenia (TE: 25%; CN: 22%), fatigue (20%; 8%), electrolyte imbalance (16%; 11%), anemia (10%; 8%), and neuropathy (8%; 8%). Grade 1-2 neuropathy occurred in 40% (TE) and 50% (CN) of pts. Two 2.5 mg/kg pts (n=34) and one 2.3 mg/kg pt (n=85) died of sepsis. 2.3 mg/kg was better tolerated than 2.5 mg/kg. CONCLUSIONS PSMA ADC was active in abi/enz refractory mCRPC pts. Clinically significant AEs included neutropenia and neuropathy. CTC conversions/reductions, PSA declines, and radiologic evidence of antitumor activity were especially noticeable in the CN population. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e1040 Peer Review Report Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.Metrics Author Information Daniel Petrylak More articles by this author Nicholas Vogelzang More articles by this author Kamal Chatta More articles by this author Mark Fleming More articles by this author David Smith More articles by this author Leonard Appleman More articles by this author Arif Hussain More articles by this author Manuel Modiano More articles by this author Parminder Singh More articles by this author Scott Tagawa More articles by this author Ira Gore More articles by this author Ed McClay More articles by this author Anthony Mega More articles by this author Oliver Sartor More articles by this author Brad Somer More articles by this author Raymond Wadlow More articles by this author Neal Shore More articles by this author Nancy Stambler More articles by this author Vincent DiPippo More articles by this author Robert Israel More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...