title: Open-label phase 1b study of FOLFIRI plus cetuximab plus IMO-2055 in patients with colorectal cancer who have progressed following chemotherapy for advanced or metastatic disease.
abstract: OBJECTIVE
  The immune modulatory oligonucleotide IMO-2055 (EMD 1201081) is a phosphorothioate oligodeoxynucleotide agonist of Toll-like receptor 9. In preclinical studies, IMO-2055 was shown to activate natural killer cells and to support the antitumor activity of monoclonal antibodies. This phase 1b, open-label, 3 + 3 dose-escalation trial was performed to determine the recommended phase 2 dose of IMO-2055 combined with FOLFIRI/cetuximab in patients with previously treated, advanced/metastatic colorectal cancer (NCT00719199).
  
  
  METHODS
  Patients received 14-day cycles of cetuximab (days 1/8; 400 mg/m(2) day 1 cycle 1, 250 mg/m(2) for subsequent days/cycles), irinotecan (day 1; 180 mg/m(2)), folinic acid (day 1; 400 mg/m(2) racemic or 200 mg/m(2) L-form), 5-fluorouracil (day 1; 400 mg/m(2) intravenous bolus, followed by 2,400 mg/m(2) as 46-h infusion), and escalating IMO-2055 doses (days 1/8; 0.16, 0.32, 0.48 mg/kg). Fifteen patients received IMO-2055, including six, three, and six patients who were treated at the dose levels 0.16, 0.32, and 0.48 mg/kg, respectively.
  
  
  RESULTS
  One dose-limiting toxicity was observed (grade 3 fatigue; at dose level 0.16 mg/kg). The most common adverse events were injection site reactions, diarrhea, fatigue, hypomagnesemia, and stomatitis. One patient achieved a confirmed partial response; 12 had stable disease, including five with stable disease ≥4.0 months.
  
  
  CONCLUSIONS
  IMO-2055 combined with FOLFIRI/cetuximab was well tolerated at all dose levels tested. IMO-2055 0.48 mg/kg was considered as the recommended phase 2 dose.
authors: Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, 2220 Pierce Avenue, 777 Preston Research Building, Nashville, TN, 37232-6307, USA, Emily.Chan@Vanderbilt.Edu.
authors: Emily
authors: E
authors: Chan
authors: Eunice L
authors: EL
authors: Kwak
authors: Jimmy
authors: J
authors: Hwang
authors: Marja
authors: M
authors: Heiskala
authors: Guillaume
authors: G
authors: de La Bourdonnaye
authors: Monica
authors: M
authors: Mita
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009841:Oligonucleotides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D051217:Toll-Like Receptor 9 / Q000819:agonists
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C587694:IMO-2055; D009841:Oligonucleotides; D051217:Toll-Like Receptor 9; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin