Phase II trial of 177lutetium radiolabeled anti-PSMA antibody J591 (177Lu-J591) for metastatic castrate-resistant prostate cancer (metCRPC): Survival update and expansion cohort with biomarkers.

Genitourinary Cancer
Session Type and Session Title: 
General Poster Session A: Prostate Cancer
Abstract Number: 
J Clin Oncol 31, 2013 (suppl 6; abstr 121)
Scott T. Tagawa, Naveed Hassan Akhtar, Joseph Osborne, Paul J. Christos, Shankar Vallabhajosula, Stanley J. Goldsmith, Renee Kahn, Caryn Ecker, Himisha Beltran, Michael J. Morris, Matthew I. Milowsky, Neil Harrison Bander, David M. Nanus; Weill Cornell Medical College, New York, NY; Memorial Sloan-Kettering Cancer Center, New York, NY; UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC

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Abstract Disclosures


Background: A phase II trial in men with progressive metCRPC receiving a single dose of 177Lu-J591 at 65 mCi/m2 (15 pts) or 70 mCi/m2 (phase I MTD, 17 pts) was performed without selection for PSMA expression, suggesting a larger than expected dose-response (13 vs 47% >30% PSA decline respectively), leading to an expansion cohort to validate the response rate at 70 mCi/m2. Methods: Endpoints: to validate the PSA and/or measurable disease response at 70 mCi/m2, evaluate circulating tumor cell counts (CellSearch) and pre-treatment PSMA imaging with 111In-J591 in the expansion cohort, and examine overall survival (OS) for all pts. Results: 15 additional pts were treated. Expansion cohort demographics were similar to the initial cohorts, and PSA responses and toxicity were similar to the initial cohort treated at 70 mCi/m2 (see Table), with myelotoxicity improving in all following nadir at 1 month. More PSA declines and longer OS were seen at 70 mCi/m2. 12 of 15 pts had baseline and follow up CTC counts at 4-6 weeks: 66.7% had >50% decline and 25% were unchanged at 0 or 1 (one declined 27%). Although 93.3% had accurate targeting (imaging) of known sites of disease, as seen in initial analysis, a trend for fewer > 30% PSA declines was seen with less intense PSMA imaging. Conclusions: Single dose 177Lu-J591 at70 mCi/m2 was generally well tolerated, with predictable, reversible myelosuppression, and demonstrates anti-tumor activity in pts with progressive metCRPC. A dose-response relationship was confirmed for both toxicity and activity, with improved response and OS at 70 mCi/m2. CTC declines are demonstrated. Selection of pts based upon non-invasive testing (PSMA imaging) may improve the therapeutic profile. Clinical trial information: NCT00195039.

Cohort Cohort 1 Cohort 2 Cohort 3 Cohorts 2+3
Dose (mCi/m2) 65 70 70 70
N 15 17 15 32
Any PSA decline 46.7% 70.6% 60.0% 65.6%
>30% PSA decline* 13.3% 47.1% 46.7% 46.9%
>50% PSA decline 6.7% 12.8% 13.3% 12.5%
Median survival*
11.9 19.8 NR 21.8
Platelets Gr 4 27% 53% 53.3% 56.3%
Platelet transfusion* 7% 41% 40.0% 40.6%
Neutropenia Gr 4* 0% 48% 26.7% 37.5%

*indicates p<0.05 for dose comparison