Originally published as JCO Early Release 10.1200/JCO.2004.09.154 on June 1 2004

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Phase I Trial of Yttrium-90—Labeled Anti—Prostate-Specific Membrane Antigen Monoclonal Antibody J591 for Androgen-Independent Prostate Cancer

From the Division of Hematology and Medical Oncology, Department of Medicine, Division of Nuclear Medicine, Department of Radiology, and Department of Urology, Weill Medical College of Cornell University, New York, NY

Address reprint requests to Neil H. Bander, MD, Weill Medical College of Cornell University, 525 E 68th St, E-300, New York, NY 10021; e-mail: nhbander{at}med.cornell.edu

PURPOSE: To determine the maximum-tolerated dose (MTD), toxicity, human antihuman antibody (HAHA) response, pharmacokinetics, organ dosimetry, targeting, and preliminary efficacy of yttrium-90–labeled anti–prostate-specific membrane antigen monoclonal antibody J591 (⁹⁰Y-J591) in patients with androgen-independent prostate cancer (PC).

PATIENTS AND METHODS: Patients with androgen-independent PC and evidence of disease progression received indium-111–J591 for pharmacokinetic and biodistribution determinations followed 1 week later by ⁹⁰Y-J591 at five dose levels: 5, 10, 15, 17.5, and 20 mCi/m². Patients were eligible for up to three re-treatments if platelet and neutrophil recovery was satisfactory.

RESULTS: Twenty-nine patients with androgen-independent PC received ⁹⁰Y-J591, four of whom were re-treated. Dose limiting toxicity (DLT) was seen at 20 mCi/m², with two patients experiencing thrombocytopenia with non–life-threatening bleeding episodes requiring platelet transfusions. The 17.5-mCi/m² dose level was determined to be the MTD. No re-treated patients experienced DLT. Nonhematologic toxicity was not dose limiting. Targeting of known sites of bone and soft tissue metastases was seen in the majority of patients. No HAHA response was seen. Antitumor activity was seen, with two patients experiencing 85% and 70% declines in prostate-specific antigen (PSA) levels lasting 8 and 8.6 months, respectively, before returning to baseline. Both patients had objective measurable disease responses. An additional six patients (21%) experienced PSA stabilization.

CONCLUSION: The recommended dose for ⁹⁰Y-J591 is 17.5 mCi/m². Acceptable toxicity, excellent targeting of known sites of PC metastases, and biologic activity in patients with androgen-independent PC warrant further investigation of ⁹⁰Y-J591 in the treatment of patients with PC.

Supported in part by National Institutes of Health General Clinical Research Center Program (NCRR grant M01RR00047); US Department of Army (DAMD17-98-1-8594); Cancer Research Institute; CaP CURE; the David H. Koch Foundation; the Peter Sacerdote Foundation; the McCoey Fund; the Laurent and Alberta Gerschel Foundation, the Yablans Family Foundation, BZL Biologics Inc; and Millennium Pharmaceuticals Inc.

Previously presented, in part, at the poster presentation of the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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