518O - Maintenance treatment with immunomodulator MGN1703 following induction with standard 1st line therapy prolongs progression-free survival in patients...

Date 01 October 2012
Event ESMO Congress 2012
Session Gastrointestinal tumors, colorectal
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Dirk Arnold
Authors D. Arnold1, H.J. Schmoll2, J. Riera-Knorrenschild3, F. Mayer4, H. Kroening5, W. Scheithauer6, D. Nitsche7, M. Tschaika8, M. Schmidt8, B. Wittig9
  • 1University Cancer Centre Hamburg, Hubertus Wald Tumour CentreKMTZ, 20246 - Hamburg/DE
  • 2Dept. Hematology/ Oncology, University of HalleMartin Luther University Hospital, DE-06120 - Halle/DE
  • 3Clinic For Hematology, Oncology And Immunology, Universitaetsklinikum Giessen und Marburg, Marburg/DE
  • 4Eberhard-Karls-Universität Tübingen, 72076 - Tübingen/DE
  • 5Schwerpunktpraxis Für Haematologie Und Onkologie, Schwerpunktpraxis für Haematologie und Onkologie, Magdeburg/DE
  • 6Oncology, Medical University of Vienna, 1090 - Vienna/AT
  • 7Innere Medizin I, Hämatologie Und Onkologie, Barmherzige Schwestern Linz, Linz/AT
  • 8Clinical Development, Mologen AG, 14195 - Berlin/DE
  • 96foundation Institute Molecular Biology And Bioinformatics, Freie Universität Berlin, Berlin/DE

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 (investigatoŕs 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.

Disclosure

M. Tschaika: Employment, stock ownership.

M. Schmidt: Employment.

B. Wittig: Stock ownership.

All other authors have declared no conflicts of interest.