Antitumor activity and safety of combination therapy with the Toll-like receptor 9 agonist IMO-2055, erlotinib, and bevacizumab in advanced or metastatic non-small cell lung cancer patients who have progressed following chemotherapy
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- Smith, D.A., Conkling, P., Richards, D.A. et al. Cancer Immunol Immunother (2014) 63: 787. doi:10.1007/s00262-014-1547-6
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IMO-2055 is a Toll-like receptor 9 (TLR9) agonist that potentially enhances the efficacy of antitumor agents through immune stimulation. The objective of this phase Ib dose-escalation trial (3 + 3 design) was to determine the recommended phase II dose (RP2D) of IMO-2055 when combined with erlotinib and bevacizumab in patients with advanced non-small cell lung cancer (NSCLC).
Patients with stage 3/4 NSCLC and progressive disease (PD) following chemotherapy received IMO-2055 0.08, 0.16, 0.32, or 0.48 mg/kg once weekly plus erlotinib 150 mg daily and bevacizumab 15 mg/kg every 3 weeks. Patients could receive treatment until PD or unacceptable toxicity.
Thirty-six patients were enrolled; 35 received at least one treatment dose. Two dose-limiting toxicities were observed across the dose range (Grade 3 dehydration and fatigue) with neither suggestive of a consistent toxicity pattern. IMO-2055 0.32 mg/kg was adopted as RP2D based on clinical and pharmacodynamic data. The most common treatment-emergent adverse events (TEAEs) were diarrhea (74 %), nausea (51 %), fatigue (51 %), rash (51 %), and injection-site reactions (49 %). Four patients experienced serious TEAEs considered to be study drug related. Five patients died, all due to PD. High-grade neutropenia and electrolyte disturbances previously reported with TLR9 agonists combined with platinum-based therapy were not observed in this study. Five of 33 patients evaluable for response (15 %) achieved partial response; another 20 (61 %) had stable disease, including 13 with stable disease ≥4 months.
IMO-2055 demonstrated good tolerability and possible antitumor activity in combination with erlotinib and bevacizumab in heavily pretreated patients with advanced NSCLC.
KeywordsAdvanced/metastatic NSCLCIMO-2055 (EMD 1201081)TLR9 agonistPhase IRecommended phase II dose
Area under the concentration–time curve from time zero to time t
Maximum plasma concentration
Eastern Cooperative Oncology Group
Epidermal growth factor receptor
Intention to treat
Medical Dictionary for Regulatory Activities
- NCI CTCAE
National Cancer Institute Common Terminology Criteria for Adverse Events
Not otherwise specified
Non-small cell lung cancer
Response Evaluation Criteria In Solid Tumors
Recommended phase II dose
Treatment-emergent adverse event
Toll-like receptor 9
Time to Cmax
Vascular endothelial growth factor