MP70-20 A PHASE 2 TRIAL OF PROSTATE SPECIFIC MEMBRANE ANTIGEN ANTIBODY DRUG CONJUGATE (PSMA ADC) IN TAXANE-TREATED METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (MCRPC) (2014)

You have accessJournal of UrologyProstate Cancer: Advanced II1 Apr 2014MP70-20 A PHASE 2 TRIAL OF PROSTATE SPECIFIC MEMBRANE ANTIGEN ANTIBODY DRUG CONJUGATE (PSMA ADC) IN TAXANE-TREATED METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (MCRPC) Daniel Petrylak, David C. Smith, Leonard J. Appleman, Mark Fleming, Arif Hussain, Robert Dreicer, A. Oliver Sartor, Neil Shore, Nicholas J. Vogelzang, Hagop Youssoufian, William Olson, Nancy Stambler, Kathleen Huang, and Robert Israel Daniel PetrylakDaniel Petrylak More articles by this author , David C. SmithDavid C. Smith More articles by this author , Leonard J. ApplemanLeonard J. Appleman More articles by this author , Mark FlemingMark Fleming More articles by this author , Arif HussainArif Hussain More articles by this author , Robert DreicerRobert Dreicer More articles by this author , A. Oliver SartorA. Oliver Sartor More articles by this author , Neil ShoreNeil Shore More articles by this author , Nicholas J. VogelzangNicholas J. Vogelzang More articles by this author , Hagop YoussoufianHagop Youssoufian More articles by this author , William OlsonWilliam Olson More articles by this author , Nancy StamblerNancy Stambler More articles by this author , Kathleen HuangKathleen Huang More articles by this author , and Robert IsraelRobert Israel More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2218AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The abundant expression of PSMA on prostate cancer cells provides a rationale for antibody therapy. PSMA ADC is a fully human antibody to PSMA linked to the microtubule disrupting agent monomethyl auristatin E (MMAE) that binds PSMA. And it internalized and cleaved by lysosomal enzymes releasing free MMAE causing cell cycle arrest and apoptosis. METHODS Seventy-five patients with progressive mCRPC progressing after taxane treatment and ECOG PS 0 or 1 were treated. PSMA ADC was administered Q3 wk IV for up to 8 cycles. Safety, tumor response by PSA, circulating tumor cells (CTC), imaging, biomarkers and clinical progression were assessed. Dosing was initiated at 2.5 mg/kg and adjustment for tolerability was allowed. RESULTS 35 pts initiated treatment at 2.5 mg/kg. Due to neutropenia, the remaining 35 pts began at 2.3 mg/kg. All pts had received prior docetaxel and abiraterone and/or enzalutamide. 41% had also received cabazitaxel. Adverse events (AEs) were consistent with those seen in phase 1; most common significant AEs were neutropenia (grade 4, 6.7% and 11.4% at 2.3 and 2.5 mg/kg, respectively) and peripheral neuropathy (grade ≥3, 6.7% (2.3) and 5.7% (2.5)). Two pts at 2.5 mg/kg died of sepsis associated with neutropenia. 47% of pts at 2.3 and 53% of pts at 2.5 had declines in CTC from ≥5 to <5 cells/7.5 ml blood and 57.1% (2.3) and 74.1% (2.5) had ≥50% CTC declines. Thus far, 26.1% (2.3) and 16.1% (2.5) have had PSA declines of ≥30%. PSA and CTC responses were associated with higher PSMA expression on CTC and lower neuroendocrine (NE) markers (NSE and CgA). The CTC conversion rate (≥5 to <5) was ∼80% in pts with low NE markers. Prior cabazitaxel or abiraterone and/or enzalutamide did not appear to affect response. Centralized assessments of images by RECIST of all pts are under evaluation and will be presented. CONCLUSIONS PSMA ADC at 2.3 mg/kg was generally well tolerated in pts with progressive mCRPC previously treated with taxanes. Antitumor activity, CTC and PSA reductions were observed at 2.3 and 2.5 mg/kg. Updated safety, tumor response and radiographic assessments from the full cohorts of 2.3 and 2.5 mg/kg will be presented. A docetaxel naiive cohort is currently accruing patients. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e813-e814 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Daniel Petrylak More articles by this author David C. Smith More articles by this author Leonard J. Appleman More articles by this author Mark Fleming More articles by this author Arif Hussain More articles by this author Robert Dreicer More articles by this author A. Oliver Sartor More articles by this author Neil Shore More articles by this author Nicholas J. Vogelzang More articles by this author Hagop Youssoufian More articles by this author William Olson More articles by this author Nancy Stambler More articles by this author Kathleen Huang More articles by this author Robert Israel More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...