Maintenance Treatment with Immunomodulator MGN1703 Following Induction with Standard 1ST Line Therapy Prolongs Progression-Free Survival in Patients with Metastatic Colorectal (MCRC): Results of the Phase II/III Impact Trial

Abstract

Introduction: Standard chemotherapy is increasingly discontinued after successful “induction” in patients ( pts) undergoing 1st line treatment for mCRC. MGN1703 is a synthetic DNA-based immunomodulator acting as an agonist of TLR-9 that has shown preclinical activity in mCRC. This study has been conducted to assess clinical efficacy, immunogenicity, and safety of MGN1703 as maintenance vs. placebo. Methods: The IMPACT study is an international, multicenter, randomized double-blind placebo-controlled phase II/III study. Pts with mCRC showing disease control (CR, PR or SD) after 4.5 to 6 months of 1st-line standard therapy with FOLFOX/XELOX or FOLFIRI +/- bevacizumab (investigators choice) were included. Results: Interim analysis of the unblinded data revealed a strong therapeutic effect compared to anticipated PFS. Therefore, patients were withheld from further randomization, according to a decision of the steering committee. In the ITT population (N = 55 pts), hazard ratio (HR) was 0.53 in favor of MGN1703 (p = 0.062). In the per-protocol population (excluding screening failures; N = 50), HR was 0.43 (p = 0.015). In the pre-defined target population (2 out of 3 factors: CEA <30 x ULN, GGT <2 x ULN, AP <2 x ULN; N = 46 pts), median PFS were 5.8 and 2.7 months for MGN1703 and placebo, respectively, with a HR at 0.39 and p = 0.013. The PFS rates after three months of treatment with MGN1703 were 43% vs. 8% (p < 0.001); after six and nine months 34% vs. 8% (p = 0.011) and 22% vs. 0% (p = 0.010) for MGN 1703 vs. placebo, respectively. Drug-related AEs included fever reported in 3 pts, atypical pneumonia, muscle aching, arthralgia, fatigue, paresthesia, rash, pruritus on injection sites, and increased ANA reported in one patient, each. Conclusions: Maintenance therapy with MGN1703 after standard chemotherapy with or without bevacizumab, is associated with significantly improved progression-free survival compared to placebo and is accompanied by low toxicity. A confirmatory clinical study in patients with metastatic CRC is currently being planned.