Preliminary results of an ongoing phase II/III clinical study of the TLR9 agonist MGN1703 in patients with advanced colorectal carcinoma with disease control after first-line induction therapy (IMPACT Study).

Abstract

618 Background: MGN1703 is a synthetic DNA-based immunomodulator, which acts as an agonist of toll-like receptor 9. The antineoplastic activity of MGN1703 was previously shown in several in-vitro and in-vivo models. A good safety profile of MGN1703 was shown in regulatory required acute and chronic toxicity studies. A currently finished phase I study in patients with metastatic solid tumors including those with CRC provided evidence for a favorable safety profile of the investigational drug as well as demonstrated positive preliminary efficacy results. Based on these promising data, a phase II/III study was initiated in patients with advanced CRC. Methods: This international multicentric randomized placebo-controlled phase II/III clinical study is being conducted in patients with advanced CRC with disease control after first-line induction therapy with standard chemotherapy regimen in combination with bevacizumab. One hundred and twenty nine patients have to be recruited to the study and randomized to be treated ether with MGN1703 or with placebo (with a ratio of 2:1), respectively. The recruited patients are treated twice a week with subcutaneous administration of 60 mg MGN1703. This dose has been proven to be safe in the phase I clinical study. The efficacy and safety of the study treatment will be evaluated based on extensive immunological tests, radiological assessment, safety laboratory results and assessments of the quality of life. The study treatment will be continued up to occurrence of tumor progression, intolerable toxicity, exclusion criteria, and withdrawal of consent or death. [Table: see text]

Trial Watch: Immunostimulation with Toll-like receptor agonists in cancer therapy

“…Schmoll and colleagues (University Clinic Halle, Halle, Germany) investigated the clinical profile of MGN1703 (a TLR9 agonist) [47][48][49] in patients with metastatic CRC achieving disease control upon standard, first-line chemotherapy. 50 Fifty-nine patients were enrolled in this Phase II, randomized, placebocontrolled study (NCT01208194), and were randomized 2:1 to receive 60 mg MGN1703 or placebo s.c., twice weekly until disease progression, withdrawal, or death.…”