Aim: To determine whether EMD 1201081, a TLR9 agonist, added to cetuximab had antitumor activity in second-line recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).
Methods: This was a phase 2, open-label, randomized trial of EMD 1201081 0.32 mg/kg subcutaneously weekly plus cetuximab (combination) vs cetuximab monotherapy (control) in cetuximab-naïve patients with R/M SCCHN who progressed on 1 cytotoxic regimen. Crossover to combination was permitted after progression.
Results: Objective response rate in both arms was 5.7% (95% CI 1.2-15.7%) by independent assessment. Disease control was 37.7% for patients on combination (24.8-52.1%) and 43.4% on control (29.8-57.7%). Neither independent nor investigator assessments showed significant differences between study arms. Median progression-free survival was 1.5 months (1.3-2.6) for patients on combination, and 1.9 months (1.5-2.9) on control. The most frequent adverse events in the combination arm were rash (29.6%), acneiform dermatitis (22.2%), and injection site reactions (20.4%). Grade 3/4 dyspnea and hypokalemia were more frequent with cetuximab monotherapy (7.5% and 5.7% vs 1.9% each, respectively), and grade 3/4 respiratory failure and disease progression were more frequent with combination (5.6% each vs 1.9% each).
Conclusion: EMD 1201081 was well tolerated combined with cetuximab, but there was no incremental clinical efficacy.
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http://dx.doi.org/10.1007/s10637-014-0117-2 | DOI Listing |
Cancer Chemother Pharmacol
April 2015
Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, 2220 Pierce Avenue, 777 Preston Research Building, Nashville, TN, 37232-6307, USA,
Purpose: 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).
View Article and Find Full Text PDFInvest New Drugs
December 2014
Zala Megyei Kórház Külsokórház Onkológia Osztály, Zalaegerszeg, Pozva, Hungary.
Aim: To determine whether EMD 1201081, a TLR9 agonist, added to cetuximab had antitumor activity in second-line recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).
Methods: This was a phase 2, open-label, randomized trial of EMD 1201081 0.32 mg/kg subcutaneously weekly plus cetuximab (combination) vs cetuximab monotherapy (control) in cetuximab-naïve patients with R/M SCCHN who progressed on 1 cytotoxic regimen.
Cancer Immunol Immunother
August 2014
Compass Oncology, 201 SE 136th Avenue, Vancouver, WA, 98684, USA,
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.
Invest New Drugs
October 2013
Service d'Oncologie Médicale, Centre du Cancer, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (IREC, MIRO), Université Catholique de Louvain, Bruxelles, Belgium,
Background: This Phase Ib trial assessed the maximum tolerated dose (MTD) and safety of the Toll-like receptor 9 agonist IMO-2055 combined with 5-fluorouracil, cisplatin, and cetuximab (PFE) as first-line palliative treatment in patients with relapsed and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).
Methods: A standard 3+3 study design was used. Patients were sequentially enrolled to be treated with IMO-2055 (0.
Biochem Soc Trans
December 2007
Idera Pharmaceuticals, 167 Sidney Street, Cambridge, MA 02139, USA.
TLRs (Toll-like receptors) are a family of innate immune receptors that induce protective immune responses against infections. Single-stranded viral RNA and bacterial DNA containing unmethylated CpG motifs are the ligands for TLR7 and TLR8 and 9 respectively. We have carried out extensive structure-activity relationship studies of DNA- and RNA-based compounds to elucidate the impact of nucleotide motifs and structures on these TLR-mediated immune responses.
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