title: A phase 1 dose-escalation study of NEO-102 in patients with refractory colon and pancreatic cancer.
abstract: OBJECTIVE
  NEO-102 is a novel chimeric IgG1 monoclonal antibody which recognizes a variant form of MUC5AC expressed specifically by human pancreatic and colorectal tumors. Preclinical models have demonstrated encouraging signs of anti-tumor activity through antibody-dependent cell-mediated cytotoxicity.
  
  
  METHODS
  This is a phase 1, dose-escalation trial of NEO-102 (Ensituximab) for patients with refractory pancreatic and colorectal cancer. The primary objective was to determine safety and tolerability of escalating doses of NEO-102. Secondary objectives were to assess pharmacokinetics, anti-tumor activity and biologic correlates. Patients whose tumors express NPC-1 antigen were eligible. Dose-escalation was performed in a 3 + 3 design at doses of 1.5, 2, 3 and 4 mg/kg.
  
  
  RESULTS
  A total of 19 patients (4 pancreatic and 15 colon cancer) were enrolled at participating institutions in the treatment phase. Most common treatment-related adverse events included anemia, fatigue, fevers, chills and flushing. There was no detectable hemolysis. Of twelve patients evaluable for disease response, the response rate at week 8 included 5 patients with stable disease and 8 patients with progressive disease (PD). Treatment-related grade 3/4 hyperbilirubinemia and anemia were observed at 4 mg/m2. Reversible hypoxia at 3 mg/kg was a dose-limiting toxicity. The maximum tolerated dose was established at 3 mg/kg. Of 74 patients who underwent tissue screening, positive NPC-1 expression was 47 % in colon and 59 % in pancreatic cancer.
  
  
  CONCLUSIONS
  Treatment with the NEO-102, in this first-in-human study, is well tolerated with a manageable safety profile. A maximum tolerated dose of 3 mg/kg has been established. Toxicity profile is typical for this therapeutic class and allows for combination with conventional cytotoxic therapies.
authors.affiliation: Division of Hematology/Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390-8852, USA. Muhammad.Beg@UTSouthwestern.edu.
authors.forename: Muhammad S
authors.initials: MS
authors.lastname: Beg
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 401 N. Broadway, Baltimore, MD, 21231, USA.
authors.forename: Nilofer S
authors.initials: NS
authors.lastname: Azad
authors.affiliation: Division of Hematology/Oncology, University of California San Diego Health System, 3855 Health Sciences Drive, La Jolla, CA, 92093, USA.
authors.forename: Sandip P
authors.initials: SP
authors.lastname: Patel
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390-8852, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Torrealba
authors.affiliation: Precision Biologics, Inc., 9700 Great Seneca Hwy, Suite 321, Rockville, MD, 20850, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Mavroukakis
authors.affiliation: Precision Biologics, Inc., 9700 Great Seneca Hwy, Suite 321, Rockville, MD, 20850, USA.
authors.forename: Melony A
authors.initials: MA
authors.lastname: Beatson
authors.affiliation: Precision Biologics, Inc., 9700 Great Seneca Hwy, Suite 321, Rockville, MD, 20850, USA.
authors.forename: Xue Ping
authors.initials: XP
authors.lastname: Wang
authors.affiliation: Precision Biologics, Inc., 9700 Great Seneca Hwy, Suite 321, Rockville, MD, 20850, USA.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Arlen
authors.affiliation: Division of Hematology/Oncology, Duke Cancer Institute, Duke University Medical Center, DUMC 384, Durham, NC, 27710, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Morse
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002352:Carrier Proteins / Q000235:genetics; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D020714:Maximum Tolerated Dose; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D000077296:Niemann-Pick C1 Protein; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; C000619852:ensituximab
keywords: Clinical trial; Colon cancer; Immunotherapy; Monoclonal antibody; Pancreatic cancer