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

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). Patients received 14-day cycles of cetuximab (days 1/8; 400 mg/m2 day 1 cycle 1, 250 mg/m2 for subsequent days/cycles), irinotecan (day 1; 180 mg/m2), folinic acid (day 1; 400 mg/m2 racemic or 200 mg/m2 l-form), 5-fluorouracil (day 1; 400 mg/m2 intravenous bolus, followed by 2,400 mg/m2 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. 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. 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.