1432TiP - Immune surveillance reactivation to improve overall survival in small cell lung cancer (SCLC): The randomized IMPULSE study

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Small-Cell Lung Cancer
Immunotherapy
Therapy
Presenter Michael Thomas
Citation Annals of Oncology (2016) 27 (6): 493-496. 10.1093/annonc/mdw389
Authors M. Thomas1, R. Carter2, S. Ponce Aix3, J. Riera-Knorrenschild4, A. Navarro Mendivil5, M. Domine6, J. Kollmeier7, P. Sadjadian8, R.M. Huber9, M. Wolf10
  • 1Internistische Onkologie Der Thoraxtumoren, Thoraxklinik Heidelberg, 69126 - Heidelberg/DE
  • 2Mologen Ag, MOLOGEN AG, 14195 - Berlin/DE
  • 3Servicio De Oncologia Medica, University Hospital 12 De Octubre, Madrid/ES
  • 4Klinik Für Innere Medizin, Klinikum der Philipps Universität Marburg, Marburg/DE
  • 5Medical Oncology, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 6Oncology, University Hospital "Fundacion Jimenez Diaz", 28040 - Madrid/ES
  • 7Klinik Für Pneumologie, HELIOS Klinikum Emil von Behring GmbH, Berlin/DE
  • 8Onkologie Und Hämatologie, Johannes Weseling klinikum, 32429 - Minden/DE
  • 9Thoracic Oncology Centre Munich, LMU Klinikum der Universität München, München/DE
  • 10Dept. Of Hemato/oncology, Klinik Kassel, 34125 - Kassel/DE

Abstract

Background

The immune surveillance reactivator lefitolimod (MGN1703), a DNA-based Toll-like receptor 9 (TLR9) agonist, was compared to placebo in metastatic CRC (mCRC) patients with disease control after standard induction chemotherapy in the double-blind randomized phase 2 IMPACT study. Lefitolimod showed a superior effect over placebo in exploratory analyses of pretreatment characteristics that identified patients most likely to benefit from lefitolimod. A study in small cell lung cancer (SCLC) patients, IMPULSE, was designed to confirm this preliminary evidence of efficacy in a new, high-mortality-and-unmet-need indication.

Trial design

Trial characteristics: IMPULSE is a randomized, international, multicenter, open-label trial to assess the effect of TLR9-mediated immune surveillance reactivation on overall survival (OS) in extensive-disease (ED) SCLC patients. Secondary endpoints include PFS, response rates, safety, and quality of life (QOL). The baseline stratification factors neuron-specific enolase (NSE) and activated NKT cells are prospectively assessed. 103 patients with objective tumor response following 4 cycles of platinum-based first-line induction therapy were randomized to receive either lefitolimod switch-maintenance therapy or local standard of care in a 3:2 ratio. Upon relapse, patients are receiving appropriate second-line therapy. All patients take part in a comprehensive immune monitoring plan that will evaluate cytokines and chemokines in serum, and the activation status of various immune cell populations. Demographic characteristics: Out of 103 patients, 62 patients were allocated to the treatment arm; 41 to standard of care (control). Median age was 63 years (MGN1703) and 64 years (control). Male/female distribution was 39/22 and 29/12, respectively. Distribution of baseline stratification factors NKT activation (≧3.5%/ 20/≦20) 11/50 and 8/33, respectively. The figures show that patients have been adequately distributed and balanced between the two treatment arms.

Clinical trial identification

2013-003503-19

Legal entity responsible for the study

MOLOGEN AG

Funding

MOLOGEN AG

Disclosure

R. Carter: Employee at MOLOGEN AG. All other authors have declared no conflicts of interest.