Prof Jorge Riera-Knorrenschild talks to ecancertv at the 1st Immunotherapy of Cancer Conference ( ITOC ) in Munich about maintenance therapy of metastatic colorectal carcinoma with the Toll-like receptor 9 (TLR-9) agonist MGN1703, including the clinical and immunological predictive pretreatment factors of activity in the IMPACT trial.

MGN1703 is a synthetic DNA-based immunomodulator acting as TLR-9 agonist which has shown preclinical activity in metastatic colorectal carcinoma (mCRC) as well as a good safety profile in patients with metastatic solid tumours in a Phase 1 trial.

The IMPACT trial was conducted to assess clinical efficacy, safety, and immunological effects of MGN1703 as maintenance therapy twice weekly s.c. vs. placebo.

There was evidence of a superior effect of MGN1703 compared with placebo. The hazard ratio (HR) for the primary endpoint PFS on maintenance treatment group was 0.55, (p=0.040) on local assessment and 0.56 (p=0.070) by independent radiological review. Notably, at time of study closure 4 patients receiving MGN1703 were still free of progression and continued treatment in compassionate use protocols. 

After induction chemotherapy for mCRC, maintenance with MGN1703 is associated with improved PFS compared to placebo and low toxicity. The team found preliminary evidence that pretreatment CEA plasma levels, tumour response and activated NKT cells counts may allow identifying patients benefiting most from MGN1703 maintenance therapy.

A confirmatory clinical study in patients with mCRC is planned to start in 2014.