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Clinical Trial
. 2014 Aug;63(8):787-96.
doi: 10.1007/s00262-014-1547-6. Epub 2014 Apr 27.

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

David A Smith  1 , Paul Conkling, Donald A Richards, John J Nemunaitis, Thomas E Boyd, Alain C Mita, Guillaume de La Bourdonnaye, David Wages, Alice S Bexon
Affiliations
Clinical Trial

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

David A Smith et al. Cancer Immunol Immunother. 2014 Aug.

Abstract

Background: 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).

Methods: 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.

Results: 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.

Conclusions: IMO-2055 demonstrated good tolerability and possible antitumor activity in combination with erlotinib and bevacizumab in heavily pretreated patients with advanced NSCLC.

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Conflict of interest statement

Thomas E. Boyd: Consultant to Celgene; research funding by Genentech, Celgene, GSK, Onyx and Pharmacyclics. Guillaume de La Bourdonnaye: Former employee of Merck KGaA (2008–2012). David Wages: Former employee of EMD Serono. Alice S. Bexon: Previously employee of Idera Pharmaceuticals, now paid consultant to Idera Pharmaceuticals. David A. Smith, Paul Conkling, Donald A. Richards, John J. Nemunaitis, and Alain C. Mita: None.

Figures

Fig. 1
Fig. 1
Mean plasma concentration–time profiles of IMO-2055 0.32 mg/kg (a), bevacizumab 15 mg/kg (b), and erlotinib 150 mg (c). Profiles are depicted in linear scale
Fig. 2
Fig. 2
Waterfall plot of best response overall per patient [changes in tumor size from baseline (%); antitumor activity evaluable population]. Four of 33 patients with measurable disease at baseline had no post-baseline tumor assessments at cycle 2
See this image and copyright information in PMC

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