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Gulec SA , Cohen SJ , Pennington KL , Zuckier LS , Hauke RJ , Horne H , Wegener WA , Teoh N , Gold DV , Sharkey RM , Goldenberg DM
Treatment of Advanced Pancreatic Carcinoma with Y-90-Clivatuzumab Tetraxetan: A Phase I Single-Dose Escalation Trial
Clinical Cancer Research. 2011 Jun;17(12) :4091-4100
PMID: ISI:000291644700025   
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Purpose: Humanized antibody hPAM4 specifically binds a mucin glycoprotein expressed in pancreatic adenocarcinomas. This phase I study evaluated a single dose of Y-90-clivatuzumab tetraxetan (Y-90-labeled hPAM4) in patients with advanced pancreatic cancer. Experimental Design: Twenty-one patients (4 stage III; 17 stage IV) received In-111-hPAM4 for imaging and serum sampling before Y-90-hPAM4. Study procedures evaluated adverse events, safety laboratories, computed tomography (CT) scans, biomarkers, pharmacokinetics, radiation dosimetry, and immunogenicity (HAHA). Results: In-111-hPAM4 showed normal biodistribution with radiation dose estimates to red marrow and solid organs acceptable for radioimmunotherapy and with tumor targeting in 12 patients. One patient withdrew before Y-90-hPAM4; otherwise, 20 patients received Y-90 doses of 15 (n = 7), 20 (n = 9), and 25 mCi/m(2) (n = 4). Treatment was well tolerated; the only significant drug-related toxicities were (NCI CTC v. 3) grade 3 to 4 neutropenia and thrombocytopenia increasing with Y-90 dose. There were no bleeding events or serious infections, and most cytopenias recovered to grade 1 within 12 weeks. Three patients at 25 mCi/m(2) encountered dose-limiting toxicity with grade 4 cytopenias more than 7 days, establishing 20 mCi/m(2) as the maximal tolerated Y-90 dose. Two patients developed HAHA of uncertain clinical significance. Most patients progressed rapidly and with CA19-9 levels increasing within 1 month of therapy, but 7 remained progression-free by CT for 1.5 to 5.6 months, including 3 achieving transient partial responses (32%-52% tumor diameter shrinkage). Conclusion: Y-90-Clivatuzumab tetraxetan was well tolerated with manageable hematologic toxicity at the maximal tolerated Y-90 dose, and is a potential new therapeutic for advanced pancreatic cancer. Clin Cancer Res; 17(12); 4091-100. (C) 2011 AACR.
Gulec, Seza A. Cohen, Steven J. Pennington, Kenneth L. Zuckier, Lionel S. Hauke, Ralph J. Horne, Heather Wegener, William A. Teoh, Nick Gold, David V. Sharkey, Robert M. Goldenberg, David M. Immunomedics, Inc. H. Horne, W.A. Wegener, N. Teoh, and D.M. Goldenberg are employed by or have financial interests with Immunomedics, Inc. S.A. Gulec, S.J. Cohen, K.L. Pennington, L.S. Zuckier, and R.J. Hauke received research support from Immunomedics, Inc. for this study. 26 Amer assoc cancer research; 615 chestnut st, 17th floor, philadelphia, pa 19106-4404 usa 777sg