Mologen AG has enrolled the first patient in the international IMPALA study. Primary objective of the phase III pivotal trial is to prove that a switch maintenance therapy with the cancer immunotherapy MGN1703 leads to an increased overall survival in patients with metastatic colorectal carcinoma. The company is a randomized, international, multicenter and controlled phase III trial expected to recruit about 540 patients from more than 100 European centers in eight European countries, including the five major pharma markets.

The primary endpoint is overall survival. Secondary study endpoints include progression-free survival, quality of life as well as safety and tolerability. Only metastatic colorectal cancer patients who have achieved a response (partial or complete response) during their first-line treatment are eligible to participate in the IMPALA study and will be randomized 1:1 to MGN1703 or local standard treatment.

Based on the evidence obtained in the IMPACT study patients will be stratified according to specific biomarkers shown after the 12-30 weeks induction therapy: normal CEA levels (tumor marker for colorectal cancer) or a certain level of activated NKT cells (Natural Killer T cells). Patients in the experimental arm will then receive 60 mg of MGN1703 mono therapy twice weekly as maintenance treatment. MGN1703 will be continued until first tumor progression.

Then the induction treatment will be restarted in combination with MGN1703. In both arms, only after second tumor progression or if no re-induction is possible for any reason, patients will stop trial treatment and start second-line therapy. The IMPALA study is supported by medical associations: Arbeitsgemeinschaft Internistische Onkologie in Germany, Grupo Espaiol de Tratamiento de Tumores Digestivos in Spain and Groupe Cooprateur Multidisciplinaire en Oncologie in France.

The steering committee consists of international medical experts; among others the coordinating study investigators Prof. David Cunningham, MD, Department of Medicine and Director of Clinical Research, Royal Marsden Hospital in London, and Prof. Dr. med. Dirk Arnold, head of Klinik for Tumorbiologie Freiburg at the Albert Ludwigs University in Freiburg. In the phase II IMPACT study, a randomized, double-blind and international trial, MGN1703 was evaluated as maintenance therapy vs.

placebo in 59 metastatic colorectal cancer patients. After study closure four patients continued on MGN1703 mono therapy treatment in compassionate use programs without progression of their disease. Three of these four patients were still progression-free for 32, 36 and 40 months as of April 2014 and continue treatment with MGN1703.

The final results on overall survival, a secondary endpoint of the IMPACT study, are still not yet mature due to a lack of events. Besides metastatic colorectal cancer, MGN1703 is being developed for first-line maintenance treatment of extensive-stage small cell lung cancer, a serious cancer disease with high unmet medical need. IMPULSE, an international randomized controlled trial, is currently enrolling patients.