1077TiP - Immunomodulatory maintenance therapy with TLR-9 agonist MGN1703 in patients with metastatic colorectal carcinoma-the randomized phase 3 IMPALA study

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Colon Cancer
Cancer Immunology and Immunotherapy
Rectal Cancer
Presenter Dirk Arnold
Citation Annals of Oncology (2014) 25 (suppl_4): iv361-iv372. 10.1093/annonc/mdu342
Authors D. Arnold1, A. Zurlo2, R. Salazar3, M. Ducreux4, T.S. Waddell5, A. Stein6, C. Tournigand7, W. Scheithauer8, A. Sobrero9, E. Van Cutsem10, D. Cunningham5
  • 1Medical Oncology, Tumor Biology Center Freiburg, 79106 - Freiburg/DE
  • 2Cmo, Mologen AG, Berlin/DE
  • 3Medical Oncology Department, Institut Català d'Oncologia Hospital Duran i Reynals, 08907 - Barcelona/ES
  • 4Oncologie Digestive, Institut de Cancérologie Gustave Roussy, 94805 - Villejuif/FR
  • 5Gi And Lymphoma Research Unit, Royal Marsden HospitalNHS Foundation Trust, London/GB
  • 6Medical Oncology, Hubertus Wald Tumor Center, University Cancer Center Hamburg (UCCH), 20246 - Hamburg/DE
  • 7Medical Oncology, Hôpital Henri Mondor, APHP, Creteil/FR
  • 8Oncology, Medical University of Vienna, 1090 - Vienna/AT
  • 9Oncologia Medica, IRCCS AOU San Martino - IST-Istituto Nazionale per la Ricerca sul Cancro, 16132 - Genova/IT
  • 10Internal Medicine, University Hospitals Leuven - Campus Gasthuisberg, 3000 - Leuven/BE

Abstract

Background

In the phase 2 IMPACT trial the potent TLR-9 agonist MGN1703, a synthetic DNA-based immunomodulator, was compared to placebo in metastatic colorectal cancer (mCRC) patients with disease control after standard induction chemotherapy +/- bevacizumab and showed a superior effect with a hazard ratio for the primary endpoint PFS on maintenance of 0.55 (p = 0.041) by local investigator assessment and 0.56 (p = 0.070) by independent radiological review. Three objective responses were observed in the MGN1703 arm, two of them appearing as late as 9 months after the start of treatment. At time of study closure 4 MGN1703 patients were still without progressive disease and continued treatment by self-administration in a compassionate use setting. Exploratory Cox regression and ROC analyses suggested a potential predictive role at baseline for normal CEA, objective response to prior chemotherapy and presence of activated NKT-cells.

Trial design

A pivotal study has been designed to confirm these data and will enroll patients with smaller tumor burden after a good response to chemotherapy, as best candidates to receive a maintenance treatment with immunotherapy. IMPALA is a randomized, international, multicenter, open-label phase 3 trial that will include 540 patients from 120 centers in Germany, Austria, Spain, Italy, France, UK, Belgium and Estonia and with the collaboration of the AIO, TTD, and GERCOR cooperative groups. In this study mCRC patients with an objective tumor response following any first line induction therapy will be randomized to MGN1703 monotherapy maintenance or local standard of care. At time of relapse, patients will reintroduce the induction treatment whenever feasible, with those in the experimental arm continuing to receive MGN1703 in the weeks without chemotherapy. Patients will also be stratified by CEA level and activated NKT at baseline. The primary endpoint of the study will be overall survival. Secondary endpoints include PFS, response rates, safety, and QoL in selected centers. All patients will be evaluated for cytokines and chemokines in serum and the activation status of various immune cell populations.

Disclosure

A. Zurlo: A.Z. is CMO of Mologen AG. All other authors have declared no conflicts of interest.