Phase I clinical study of the toll-like receptor 9 agonist MGN1703 in patients with metastatic solid tumours. Issue 2 (January 2015)

• Record Type: Journal Article
• Authors: Weihrauch, Martin R.; Richly, Heike; von Bergwelt-Baildon, Michael S.; Becker, Hans Jiro; Schmidt, Manuel; Hacker, Ulrich T.; Shimabukuro-Vornhagen, Alexander; Holtick, Udo; Nokay, Bahar; Schroff, Matthias; Wittig, Burghardt; Scheulen, Max E.
• Is Part Of: European journal of cancer. Volume 51:Issue 2(2015:Jan.)
• Page Start: 146
• Page End: 156
• Publication Date: 2015-01
• Subjects: Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2014.11.002
• Languages: English
• ISSNs: 0959-8049

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab010"> <title id="st170">Abstract</title> <sec> <title id="st125">Purpose</title> <p id="sp0010">This study was initiated to evaluate safety, toxicity, pharmacokinetics, and pharmacodynamics of treatment with MGN1703, a novel synthetic DNA-based toll-like receptor 9 (TLR9)-immunomodulator.</p> </sec> <sec> <title id="st130">Methods</title> <p id="sp0015">The study consisted of an escalating single dose regimen followed by a multiple dose part. Dose levels of 0.25, 2, 10, 30, and 60 mg of MGN1703 were administered subcutaneously over 6 weeks twice weekly. Patients with at least stable disease (SD) could participate in the extension phase of the study for six further weeks. Effects on the immune status were monitored.</p> </sec> <sec> <title id="st135">Results</title> <p id="sp0020">28 patients with metastatic solid tumours were included. Fatigue and activated partial thromboplastin time (aPTT) prolongation were the only two cases of drug-related grade 3 Common Terminology Criteria adverse events (CTCAE). The most frequently reported drug-related adverse events were of CTC Grade ⩽2. There was no relationship between toxicity and dose and no patient was withdrawn from the study due to drug-related AE. No drug-related serious AE (SAE) were reported. Six out of 24 patients had SD after 6 weeks of treatment and three of those remained in SD after a total of 12 weeks. Four patients were further treated in a compassionate use programme showing long-term disease stabilisation for up to 18 months. Immune assessment of cell compartments showed a non-significant increase of TLR9 expressing naïve B cells during therapy.</p> </sec> <sec> <title id="st140">Conclusion</title> <p id="sp0070">Twice weekly subcutaneous applications of MGN1703 in a dose of up to 60 mg are safe and well tolerated without dose-limiting toxicities. MGN1703 shows immune activation and anti-tumour efficacy in heavily pretreated patients. The recommended dose of 60 mg twice weekly is currently used in a phase II trial in small cell lung cancer and a phase III trial in colorectal cancer patients.</p> </sec> </abstract>