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Clinical Trial
. 2013 Sep 15;19(18):5182-91.
doi: 10.1158/1078-0432.CCR-13-0231. Epub 2013 May 28.

Phase II study of Lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate cancer

Scott T Tagawa  1 , Matthew I Milowsky, Michael Morris, Shankar Vallabhajosula, Paul Christos, Naveed H Akhtar, Joseph Osborne, Stanley J Goldsmith, Steve Larson, Neeta Pandit Taskar, Howard I Scher, Neil H Bander, David M Nanus
Affiliations
Clinical Trial

Phase II study of Lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for metastatic castration-resistant prostate cancer

Scott T Tagawa et al. Clin Cancer Res. .

Abstract

Purpose: To assess the efficacy of a single infusion of radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 (lutetium-177; (177)Lu) by prostate-specific antigen (PSA) decline, measurable disease response, and survival.

Experimental design: In this dual-center phase II study, two cohorts with progressive metastatic castration-resistant prostate cancer received one dose of (177)Lu-J591 (15 patients at 65 mCi/m(2), 17 at 70 mCi/m(2)) with radionuclide imaging. Expansion cohort (n = 15) received 70 mCi/m(2) to verify response rate and examine biomarkers.

Results: Forty-seven patients who progressed after hormonal therapies (55.3% also received prior chemotherapy) received (177)Lu-J591. A total of 10.6% experienced ≥50% decline in PSA, 36.2% experienced ≥30% decline, and 59.6% experienced any PSA decline following their single treatment. One of 12 with measurable disease experienced a partial radiographic response (8 with stable disease). Sites of prostate cancer metastases were targeted in 44 of 47 (93.6%) as determined by planar imaging. All experienced reversible hematologic toxicity, with grade 4 thrombocytopenia occurring in 46.8% (29.8% received platelet transfusions) without significant hemorrhage. A total of 25.5% experienced grade 4 neutropenia, with one episode of febrile neutropenia. The phase I maximum tolerated dose (70 mCi/m(2)) resulted in more 30% PSA declines (46.9% vs. 13.3%, P = 0.048) and longer survival (21.8 vs. 11.9 months, P = 0.03), but also more grade 4 hematologic toxicity and platelet transfusions. No serious nonhematologic toxicity occurred. Those with poor PSMA imaging were less likely to respond.

Conclusion: A single dose of (177)Lu-J591 was well tolerated with reversible myelosuppression. Accurate tumor targeting and PSA responses were seen with evidence of dose response. Imaging biomarkers seem promising.

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Conflict of interest statement

Conflict of interest: NHB is an inventor on patents that are assigned to Cornell Research Foundation (“CRF”) for the J591 antibody described in this article. Dr. Bander is a paid consultant to and owns stock in BZL Biologics, the company to which the patents were licensed by CRF for further research and development.

Figures

Figure 1
Figure 1
PSA waterfall plot Each individual subject’s best PSA response on study. Those subjects treated with 65 mCi/m2 of 177Lu-J591 (Cohort 1) are indicated in light gray while those that received 70 mCi/m2 of 177Lu-J591 (the phase I trial maximum tolerated dose) are indicated in blue (Cohort 2) or red (Cohort 3).
Figure 2
Figure 2
Overall survival Probability of survival by dose received. [OS:overall survival; mo: months]
Figure 3
Figure 3
Imaging Left: 99mTc-MDP bone scan: Anterior (A) and posterior (B) images of pretreatment bony metastases. Right: 177Lu-J591 scan: Anterior (C) and posterior (D) total body images obtained via dual head gamma camera of sites of uptake 7 days after 177Lu-J591 administration. (Note: Radiolabeled antibody is partially cleared via the liver resulting in non-specific 177Lu localization).
See this image and copyright information in PMC

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