14TiP - Immunomodulatory switch maintenance therapy to improve overall survival in small cell lung cancer (SCLC): The randomized IMPULSE study

Date 20 November 2015
Event ESMO Symposium on Immuno-Oncology 2015
Session Welcome reception and general Poster viewing
Topics Small-Cell Lung Cancer
Cancer Immunology and Immunotherapy
Citation Annals of Oncology (2015) 26 (suppl_8): 5-14. 10.1093/annonc/mdv514
Authors A. Zurlo1, R. Carter1, S. Ponce Aix2, J. Riera Knorrenschild3, A. Navarro Mendivil4, M. Domine5, J. Kollmeier6, R.M. Huber7
  • 1Clinical Development, MOLOGEN AG, 14195 - Berlin/DE
  • 2Servicio De Oncologia Medica, University Hosptial 12 De Octubre, 28041 - Madrid/ES
  • 3Klinikum, Klinikum der Philipps-Universität Marburg, 35043 - Marburg/DE
  • 4Institut D'oncologia, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 5Oncology, University Hospital "Fundacion Jimenez Diaz", 28040 - Madrid/ES
  • 6Onkologie, 7HELIOS Klinikum Emil von Behring GmbH, 14165 - Berlin/DE
  • 7Thoracic Oncology Centre Munich, LMU Klinikum der Universität München, 80336 - München/DE

Abstract

Background

The immunomodulator MGN1703, a DNA-based Toll-Like Receptor 9 (TLR-9) agonist, was compared to placebo in mCRC patients with disease control after standard induction CT +/- bev in a double-blind randomized phase 2 study. The drug was given as switch maintenance in 59 patients not progressing after 4.5 - 6 months of 1st line induction, since MGN1703 postulates the need of free circulating tumor-associated antigens to activate the immune system. MGN1703 showed a superior effect over placebo, with a hazard ratio (HR) for the primary endpoint PFS on maintenance of 0.55 (p = 0.041). Patients with objective RECIST response, normal carcinoembryonic antigen and presence of activated natural killer T cells benefited the most from MGN1703 maintenance. Overall Survival (OS) after induction therapy had an HR of 0.40 (24.5 vs. 15.1 months). By study end, 4 MGN1703 patients still without PD continued treatment in compassionate use. An update in August 2015 showed 3 patients still receiving MGN1703 without relapse for 47-55 months. A study in extensive-disease SCLC patients in response after first line platinum therapy was designed to confirm this evidence.

Trial design

IMPULSE is a randomized international open-label trial with participation of the German ABC group. 100 SCLC patients with tumor response following 4 cycles of platinum-based first line induction are randomized 3:2 to receive MGN1703 switch maintenance therapy (experimental), or local standard of care (control). In case of relapse on maintenance or control, patients receive appropriate second-line therapy. The primary endpoint of the study is OS. Secondary endpoints are PFS, safety, and QoL. Neuron-specific enolase and activated NKT at baseline are stratification factors and are prospectively assessed. All randomized patients take part in a comprehensive immune monitoring plan evaluating cytokines and chemokines and the activation status of immune cell populations. Begun in 4/14, recruitment is ongoing in 4 European countries and will be completed in Q3-4 2015.

Clinical trial identification

NCT02200081

First received: January 9, 2014

Disclosure

M. Thomas: Scientific committee IMPULSE trial. A. Zurlo: CMO of Mologen AG. R. Carter: Medical Director at Mologen AG. S. Ponce Aix, J. Riera Knorrenschild, M. Domine, J. Kollmeier and A. Navarro Mendivil: Principal investigators IMPULSE trial. R.M. Huber: Steering committee member IMPULSE trial. M. Wolf: Member scientific committee IMPULSE TRIAL.