Date: 2016-02-25
Type of information: update on patient enrollment
phase: 3
Announcement: update
Company: Mologen (Germany)
Product: MGN1703 (lefitolimod)
Action
mechanism: immunotherapy product/TLR9 agonist. Lefitolimod (MGN1703) is based on dSLIM® (“double Stem Loop Immunomodulator”), a DNA-based TLR9 agonist developed by Mologen. dSLIM® activates the immune system against tumor-associated antigens by targeting various receptors on certain immune cells, primarily TLR9. Tumor-associated antigens (TAA) are released by cancer cells as a result of chemotherapy and radiation therapy. Once activated by dSLIM®, the immune system is able to overcome its fatal tolerance toward cancer cells and TAA and attacks them selectively. Treatment with lefitolimod (MGN1703) triggers a broad and strong activation of the immune system. Due to this mechanism of action, lefitolimod (MGN1703) has the potential to be applied to various indications.
Disease: colorectal cancer
Therapeutic area: Cancer - Oncology
Country: Austria, Belgium, Estonia, France, Germany, Italy, Spain, UK
Trial
details: IMPALA (Immunomodulatory MGN1703 in Patients with Advanced Colorectal Carcinoma with tumor reduction during induction treatment) is an international phase III, randomized, open-label, two-arms, and multicenter clinical study. The trial will include patients with metastatic colorectal cancer who had tumor reduction after receiving first-line chemotherapy with or without biological agents. The study will include around 540 patients in eight European countries from more than 100 centers, including the five major European pharma markets.The primary endpoint is overall survival and secondary study endpoints include progression-free survival from start of induction therapy, toxicity and safety, and Quality of Life (QoL). (NCT02077868) The IMPALA study is supported by leading medical associations: Arbeitsgemeinschaft Internistische Onkologie (AIO) in Germany, Grupo Españiol de Tratamiento de Tumores Digestivos (TTD) in Spain and Groupe Coopérateur Multidisciplinaire en Oncologie (GERCOR) 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 für Tumorbiologie Freiburg at the Albert Ludwigs University in Freiburg.
Latest
news: * On February 25, 2016, Mologen announced that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has confirmed the development strategy of lefitolimod (MGN1703) with the pivotal IMPALA study by scientific advice. IMPALA study aims to prove that a switch maintenance therapy with an active immunotherapy leads to an increased overall survival of patients who have achieved a response during their first line treatment of metastatic colorectal cancer. The primary endpoint is overall survival and secondary study endpoints include progression-free survival, toxicity and safety, and Quality of Life (QoL). Recruitment of the IMPALA study started in September 2014 and is expected to enroll 540 patients in 8 European countries. Patient recruitment is expected to be completed by the end of 2016. * On September 11, 2014, Mologen 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 (OS) in patients with metastatic colorectal carcinoma. 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). The IMPALA trial is based on the data from the phase II study IMPACT presented at ESMO World Congress on Gastrointestinal Cancer in July 2013. The study was chosen by ESMO to be among the most important contributions of the conference. The final analysis provided proof-of-concept evidence for MGN1703 in terms of efficacy and safety. The pivotal phase III international trial is to confirm these results in a larger number of patients. The design of the phase III study IMPALA will be presented at the ESMO 16th World Congress in Gastrointestinal (GI) Cancer 2014 in Barcelona, Spain, from 25-28 June 2014.
Patients in the experimental arm will then receive 60mg of MGN1703 monotherapy twice weekly as maintenance treatment. MGN1703 will be continued until first tumor progression. Then the induction treatment will be restarted in combination with MGN1703. Patients in the control arm will receive any local maintenance treatment regimen. They may either continue induction therapy, halt some of the agents or interrupt all therapies. After first tumor progression the induction therapy will be restarted.
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.
* On May 5, 2014, Mologen has started to submit clinical trial applications for MGN1703 in metastatic colorectal cancer to the competent authorities in Europe. The applications will also be submitted to the responsible ethics committees. The pivotal phase III clinical trial IMPALA is designed as an open-label, two-arms, randomized, controlled and multicenter study. The aim of the study is to evaluate the efficacy of the first-line maintenance treatment with MGN1703 in patients with metastatic colorectal cancer. The primary endpoint of the study is to determine patient overall survival. It is planned to include patients from more than 100 sites in eight European countries, including the five major European pharma markets. In addition, three renowned national cancer associations will participate in the IMPALA trial and contribute their specific expertise: Arbeitsgemeinschaft Internistische Onkologie (AIO) in Germany, Grupo Españiol de Tratamiento de Tumores Digestivos (TTD) in Spain and Groupe Coopérateur Multidisciplinaire en Oncologie (GERCOR) in France. Mologen expects to start first patient enrollment in the second half of 2014, directly after receipt of the necessary approvals. The coordinating study investigators are Prof. David Cunningham, MD, Department of Medicine and Director of Clinical Research, Royal Marsden Hospital in London, and Prof. Dirk Arnold, head of Klinik für Tumorbiologie Freiburg at the Albert Ludwigs University in Freiburg. They are members of the international steering committee* of the IMPALA study among other leading experts in gastrointestinal oncology in Europe.
