title: A phase I study of IMP321 and gemcitabine as the front-line therapy in patients with advanced pancreatic adenocarcinoma.
abstract: OBJECTIVE
  This phase I study was conducted to determine the safety profile and maximum tolerated dose (MTD) of IMP321, a soluble lymphocyte activation gene-3 (LAG-3) Ig fusion protein and MHC Class II agonist, combined with gemcitabine in patients with advanced pancreatic adenocarcinoma.
  
  
  METHODS
  Patients with advanced pancreatic adenocarcinoma were treated with gemcitabine (1,000 mg/m(2))(level 1), gemcitabine (1,000 mg/m(2)) plus IMP 321 at 0.5 mg (level 2) and 2.0 mg (level 3), respectively. Safety, toxicity, and immunological markers at baseline and post treatment were assessed.
  
  
  RESULTS
  A total of 18 patients were enrolled to the study, and 17 were evaluable for toxicity. None of the 6 patients who received 0.5 mg IMP321 experienced IMP321-related adverse events. Of the 5 patients who received IMP321 at the 2 mg dose level, 1 experienced rash, 1 reported hot flashes and 2 had mild pain at the injection sites. No severe adverse events previously attributed to IMP321 were observed. No significant differences were observed when comparing pre- and post-treatment levels of monocytes (CD11b+CD14+), conventional dendritic cells (CD11c+) or T cell subsets (CD4, CD8).
  
  
  CONCLUSIONS
  IMP321 in combination with gemcitabine is a well-tolerated regimen. IMP321 did not result in any severe adverse events. No incremental activity observed for the additional IMP 321 to gemcitabine at the dose levels evaluated, likely due to sub-optimal dosing. Immunological markers suggested that higher dose levels of IMP321 are needed for future clinical studies.
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Wang-Gillam
authors.forename: Stacey
authors.initials: S
authors.lastname: Plambeck-Suess
authors.forename: Peter
authors.initials: P
authors.lastname: Goedegebuure
authors.forename: Peter O
authors.initials: PO
authors.lastname: Simon
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Mitchem
authors.forename: John R
authors.initials: JR
authors.lastname: Hornick
authors.forename: Steven
authors.initials: S
authors.lastname: Sorscher
authors.forename: Joel
authors.initials: J
authors.lastname: Picus
authors.forename: Rama
authors.initials: R
authors.lastname: Suresh
authors.forename: Albert C
authors.initials: AC
authors.lastname: Lockhart
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tan
authors.forename: Williams G
authors.initials: WG
authors.lastname: Hawkins
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine; D000093322:Lymphocyte Activation Gene 3 Protein; C000720328:soluble LAG-3 protein, human; C000720326:Lag3 protein, human