title: Novel Treatment with Intraperitoneal MOC31PE Immunotoxin in Colorectal Peritoneal Metastasis: Results From the ImmunoPeCa Phase 1 Trial.
abstract: BACKGROUND
  MOC31PE immunotoxin was developed to rapidly kill cells expressing the tumor-associated epithelial cell adhesion molecule, which is highly expressed in colorectal cancer. Although cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may offer long-term survival to patients with peritoneal metastasis from colorectal cancer (PM-CRC), most patients experience disease relapse and novel therapeutic options are needed. On this basis, MOC31PE is being developed as a novel therapeutic principle to target PM-CRC.
  
  
  METHODS
  This was a dose-escalating phase I trial to evaluate the safety and toxicity (primary endpoint), pharmacokinetic profile, and neutralizing antibody response (secondary endpoints) upon intraperitoneal administration of MOC31PE in patients with PM-CRC undergoing CRS-HIPEC with Mitomycin C. Fifteen patients received the study drug at four dose levels (3+3+3+6), administered intraperitoneally as a single dose the day after CRS-HIPEC.
  
  
  RESULTS
  No dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. There was negligible systemic absorption of the study drug. Drug concentrations in peritoneal fluid samples were in the cytotoxic range and increased in a dose-dependent manner. MOC31PE recovered from peritoneal cavity retained its cytotoxic activity in cell-based assays. All patients developed neutralizing antibodies.
  
  
  CONCLUSIONS
  Intraperitoneal administration of MOC31PE was safe and well tolerated, and combined with low systemic uptake, MOC31PE seems ideal for local intraperitoneal treatment. The drug will be further evaluated in an ongoing phase II expansion cohort.
authors.affiliation: Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.|Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ida S
authors.initials: IS
authors.lastname: Frøysnes
authors.affiliation: Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Andersson
authors.affiliation: Department of Gastroenterological Surgery, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Stein G
authors.initials: SG
authors.lastname: Larsen
authors.affiliation: Faculty of Medicine, University of Oslo, Oslo, Norway.|Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
authors.affiliation: Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Janne-Merete Torset
authors.initials: JT
authors.lastname: Øien
authors.affiliation: Department of Medical Biochemistry, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Kari Hauge
authors.initials: KH
authors.lastname: Olsen
authors.affiliation: Faculty of Medicine, University of Oslo, Oslo, Norway.|Department of Gastroenterological Surgery, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Giercksky
authors.affiliation: Department of Radiology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Julsrud
authors.affiliation: Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.|Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Fodstad
authors.affiliation: Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Svein
authors.initials: S
authors.lastname: Dueland
authors.affiliation: Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. kjersti.flatmark@rr-research.no.|Faculty of Medicine, University of Oslo, Oslo, Norway. kjersti.flatmark@rr-research.no.|Department of Gastroenterological Surgery, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. kjersti.flatmark@rr-research.no.
authors.forename: Kjersti
authors.initials: K
authors.lastname: Flatmark
mesh_terms: D000328:Adult; D000368:Aged; D018279:Carcinoma, Signet Ring Cell / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D014018:Tissue Distribution
chemical_list: D018796:Immunoconjugates; C000602279:MOC31PE immunotoxin