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.