title: Treatment of advanced pancreatic carcinoma with 90Y-Clivatuzumab Tetraxetan: a phase I single-dose escalation trial.
abstract: OBJECTIVE
  Humanized antibody hPAM4 specifically binds a mucin glycoprotein expressed in pancreatic adenocarcinomas. This phase I study evaluated a single dose of (90)Y-clivatuzumab tetraxetan ((90)Y-labeled hPAM4) in patients with advanced pancreatic cancer.
  
  
  METHODS
  Twenty-one patients (4 stage III; 17 stage IV) received (111)In-hPAM4 for imaging and serum sampling before (90)Y-hPAM4. Study procedures evaluated adverse events, safety laboratories, computed tomography (CT) scans, biomarkers, pharmacokinetics, radiation dosimetry, and immunogenicity (HAHA).
  
  
  RESULTS
  (111)In-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 (90)Y-hPAM4; otherwise, 20 patients received (90)Y 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 (90)Y 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 (90)Y 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).
  
  
  CONCLUSIONS
  (90)Y-Clivatuzumab tetraxetan was well tolerated with manageable hematologic toxicity at the maximal tolerated (90)Y dose, and is a potential new therapeutic for advanced pancreatic cancer.
authors.affiliation: Goshen Center for Cancer Care, Goshen, Indiana, USA.
authors.forename: Seza A
authors.initials: SA
authors.lastname: Gulec
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Cohen
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Pennington
authors.forename: Lionel S
authors.initials: LS
authors.lastname: Zuckier
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Hauke
authors.forename: Heather
authors.initials: H
authors.lastname: Horne
authors.forename: William A
authors.initials: WA
authors.lastname: Wegener
authors.forename: Nick
authors.initials: N
authors.lastname: Teoh
authors.forename: David V
authors.initials: DV
authors.lastname: Gold
authors.forename: Robert M
authors.initials: RM
authors.lastname: Sharkey
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D002277:Carcinoma / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011859:Radiography; D011874:Radiometry; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor