- Email: [email protected]
ENZ): RESULTS FROM A PHASE 2 STUDY
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THE JOURNAL OF UROLOGYâ
associated with adverse pathology. In Cox regression multivariate model, there was no significant prognostic factor which anticipates the postoperative biochemical recurrence of these active surveillance candidates. CONCLUSIONS: In PRIAS criteria, there was no significant difference of biochemical recurrence according to pGS upgrading or adverse pathologic feature. Large scale-multicenter prospective study will be required in the future.
Vol. 193, No. 4S, Supplement, Tuesday, May 19, 2015
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 Daniel Petrylak*, New Haven, CT; Nicholas Vogelzang, Las Vegas, NV; Kamal Chatta, Seattle, WA; Mark Fleming, Norfolk, VA; David Smith, Ann Arbor, MI; Leonard Appleman, Pittsburgh, PA; Arif Hussain, Baltimore, MD; Manuel Modiano, Parminder Singh, Tucson, AZ; Scott Tagawa, New York, NY; Ira Gore, Birmingham, AL; Ed McClay, Encinitas, CA; Anthony Mega, Providence, RI; Oliver Sartor, New Orleans, LA; Brad Somer, Memphis, TN; Raymond Wadlow, Fairfax, VA; Neal Shore, Myrtle Beach, SC; Nancy Stambler, Vincent DiPippo, Robert Israel, Tarrytown, NY 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 (n¼113); CTC counts showed a decline of 50% in 78% of pts and conversion from 5 to <5 cells/7.5 ml blood in 47% (n¼77) at any time during the study. For 2.3 mg/kg pts (n¼82), corresponding PSA declines were 35% and 17%; CTC declines of 50% were seen in 81% and conversions in 46% (n¼54). For CN pts, PSA declines of 30% and 50% were 31% and 20% (n¼35) vs. 29% and 12% in TE pts (n¼78). CTC declines of 50% were seen in 89% and conversion in 53% (n¼19; CN) vs. 74% and 45% (n¼58; 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 (n¼34) and one 2.3 mg/kg pt (n¼85) 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. Source of Funding: This study was funded by Progenics Pharmaceuticals, Inc., which has a proprietary commercial interest in PSMA ADC.
MP82-10 PSMA-RADIOGUIDED SURGERY: INTRODUCING MOLECULAR SURGERY IN PATIENTS WITH RECURRENT PROSTATE CANCER €rgen Wester, Tobias Maurer*, Martina Weineisen, Hans-Ju € bler, Margret Schottelius, Asli Okur, Gregor Weirich, Hubert Ku € rgen Erich Gschwend, Benjamin Frisch, Markus Schwaiger, Ju Matthias Eiber, Munich, Germany
Source of Funding: none
INTRODUCTION AND OBJECTIVES: With the advent of 68Ga-HBED-PSMA PET hybrid imaging techniques even small and atypical localized metastatic lesions of prostate cancer (PCa) can be
THE JOURNAL OF UROLOGYâ
associated with adverse pathology. In Cox regression multivariate model, there was no significant prognostic factor which anticipates the postoperative biochemical recurrence of these active surveillance candidates. CONCLUSIONS: In PRIAS criteria, there was no significant difference of biochemical recurrence according to pGS upgrading or adverse pathologic feature. Large scale-multicenter prospective study will be required in the future.
Vol. 193, No. 4S, Supplement, Tuesday, May 19, 2015
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 Daniel Petrylak*, New Haven, CT; Nicholas Vogelzang, Las Vegas, NV; Kamal Chatta, Seattle, WA; Mark Fleming, Norfolk, VA; David Smith, Ann Arbor, MI; Leonard Appleman, Pittsburgh, PA; Arif Hussain, Baltimore, MD; Manuel Modiano, Parminder Singh, Tucson, AZ; Scott Tagawa, New York, NY; Ira Gore, Birmingham, AL; Ed McClay, Encinitas, CA; Anthony Mega, Providence, RI; Oliver Sartor, New Orleans, LA; Brad Somer, Memphis, TN; Raymond Wadlow, Fairfax, VA; Neal Shore, Myrtle Beach, SC; Nancy Stambler, Vincent DiPippo, Robert Israel, Tarrytown, NY 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 (n¼113); CTC counts showed a decline of 50% in 78% of pts and conversion from 5 to <5 cells/7.5 ml blood in 47% (n¼77) at any time during the study. For 2.3 mg/kg pts (n¼82), corresponding PSA declines were 35% and 17%; CTC declines of 50% were seen in 81% and conversions in 46% (n¼54). For CN pts, PSA declines of 30% and 50% were 31% and 20% (n¼35) vs. 29% and 12% in TE pts (n¼78). CTC declines of 50% were seen in 89% and conversion in 53% (n¼19; CN) vs. 74% and 45% (n¼58; 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 (n¼34) and one 2.3 mg/kg pt (n¼85) 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. Source of Funding: This study was funded by Progenics Pharmaceuticals, Inc., which has a proprietary commercial interest in PSMA ADC.
MP82-10 PSMA-RADIOGUIDED SURGERY: INTRODUCING MOLECULAR SURGERY IN PATIENTS WITH RECURRENT PROSTATE CANCER €rgen Wester, Tobias Maurer*, Martina Weineisen, Hans-Ju € bler, Margret Schottelius, Asli Okur, Gregor Weirich, Hubert Ku € rgen Erich Gschwend, Benjamin Frisch, Markus Schwaiger, Ju Matthias Eiber, Munich, Germany
Source of Funding: none
INTRODUCTION AND OBJECTIVES: With the advent of 68Ga-HBED-PSMA PET hybrid imaging techniques even small and atypical localized metastatic lesions of prostate cancer (PCa) can be