Maintenance treatment with MGN1703 following standard first-line treatment prolongs progression-free survival in patients with metastatic colorectal cancer

A role of immunomodulation after successful first-line treatment

MGN1703 is a synthetic DNA-based immunomodulator with TLR-9 agonist activity. The results of the study on maintenance therapy with MGN1703 following successful standard first-line treatment in patients with metastatic colorectal cancer (mCRC) were reported by Dr Dirk Arnold at the proffered papers session of the Gastrointestinal, Colorectal Cancer programme track of the ESMO 2012 Congress in Vienna.

The phase II/III IMPACT study evaluated the clinical efficacy, immunogenicity and safety of MGN1703 compared to placebo in patients with mCRC who achieved complete response (CR), partial response (PR) or stable disease (SD) following 4.5 to 6 months of first-line standard therapy with FOLFOX/XELOX or FOLFIRI, both with and without bevacizumab (investigator´s choice).

Randomization following enrolment was halted after interim analysis of unblinded data demonstrated a strong therapeutic effect with MGN1703; the hazard ratio (HR) was 0.53; p = 0.062 in 55 patients comprising the intent to treat population. In the per-protocol population, which excluded screening failures and contained 50 patients the HR was 0.43; p = 0.015, again favouring MGN1703.

Progression-free survival (PFS) in the pre-defined target population of 46 patients (2 out of 3 factors: CEA <30 x ULN, GGT <2 x ULN, AP <2 x ULN) was 5.8 months with MGN1703 compared to 2.7 months with placebo, HR 0.39; p = 0.013. Following three months of treatment, PFS rates were 43% with MGN1703 and 8% with placebo (p < 0.001); after six months rates were 34% compared to 8% (p = 0.011) and at nine months PFS rates were 22% compared to 0% (p = 0.010) for MGN1703 and placebo, respectively.

The treatment was well tolerated with low toxicity. Drug-related adverse events included fever, atypical pneumonia, muscle aching, arthralgia, fatigue, paresthesia, rash, pruritus on injection sites, and increased ANA.

A confirmatory clinical study in patients with mCRC is being initiated to elaborate on the results of significantly prolonged progression-free survival associated with MGN1703 compared to placebo in patients who successfully completed standard chemotherapy with or without bevacizumab. The treatment with MGN1703 in the IMPAKT phase II/III study was accompanied by low toxicity.