1527O - Top-line data from the randomized phase 2 IMPULSE study in small-cell lung cancer (SCLC): Immunotherapeutic maintenance treatment with lefitolimod

Date 10 September 2017
Event ESMO 2017 Congress
Session Mesothelioma and SCLC
Topics Small-Cell Lung Cancer
Cancer Immunology and Immunotherapy
Lung and other Thoracic Tumours
Presenter Michael Thomas
Citation Annals of Oncology (2017) 28 (suppl_5): v539-v542. 10.1093/annonc/mdx386
Authors M. Thomas1, S. Ponce-Aix2, A. Navarro Mendivil3, J. Riera Knorrenschild4, M. Schmidt5, M. Krikow6, E. Wiegert6, M. Domine Gomez7, J. Kollmeier8, P. Sadjadian9, K.P. Fröhling10, R.M. Huber11, M. Wolf12
  • 1Oncology, Thoraxklinik at the Heidelberg University Medical Center and Translational Lung Research Center Heidelberg (TLRC-H), The German Center for Lung Research (DZL), 69126 - Heidelberg/DE
  • 2Medical Oncology, Hospital 12 de Octubre, Madrid/ES
  • 3Vall D' Hebron Institute Of Research (vhir), Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 4Hämatologie, Onkologie Und Immunologie, Klinikum der Philipps Universität Marburg, Marburg/DE
  • 5Translational Research, Mologen AG, 14195 - Berlin/DE
  • 6Clinical Department, Mologen AG, 14195 - Berlin/DE
  • 7Medical Oncology, University Hospital "Fundacion Jimenez Diaz", 28040 - Madrid/ES
  • 8Klinik Für Pneumologie, HELIOS Klinikum Emil von Behring GmbH, Berlin/DE
  • 9Abteilung Pneumologie, Johannes Weseling Klinikum, 32429 - Minden/DE
  • 10Pneumologie, Kath. Klinikum Koblenz-Montabaur, Koblenz/DE
  • 11Division Of Respiratory Medicine And Thoracic Oncology, University Hospital of Munich, Munich/DE
  • 12Medizinische Klinik Iv, Klinikum Kassel, 34125 - Kassel/DE

Abstract

Background

The immune surveillance reactivator lefitolimod (MGN1703), a DNA-based TLR9 agonist, is currently in a comprehensive clinical development program including a phase 3 trial in mCRC. The phase 2 IMPULSE study was designed to evaluate the efficacy and safety of lefitolimod in small-cell lung cancer (SCLC).

Methods

IMPULSE is a randomized, international, multicenter, open-label trial to assess the effect of lefitolimod-mediated immune surveillance reactivation on overall survival (OS) in extensive-disease SCLC. 102 patients with objective tumor response following 4 cycles of platinum-based first-line induction therapy were randomized 3:2 to receive either lefitolimod maintenance therapy or local standard of care (control). Upon relapse, patients have received appropriate second-line therapy.

Results

Out of 102 patients, 61 were randomized to the lefitolimod, 41 to the control arm. Distribution of patients to the two arms was balanced regarding patient demographics. Even though in this highly challenging indication the primary endpoint OS of the overall study population was not met, IMPULSE showed positive results in two pre-defined and clinically relevant subgroups: An OS benefit was shown in comparison with the control arm in patients with a low count of activated CD86+ B cells (HR 0.59, 95%CI 0.29-1.21, n = 38 of 88) as well as in patients with reported chronic obstructive pulmonary disease (COPD), (HR 0.54, 95%CI 0.21-1.38, n = 25 of 102). Immunologic parameters confirmed lefitolimod’s mode-of-action with a clear activation of CD169+ monocytes and production of IP-10 in response to lefitolimod treatment. Lefitolimod showed a favorable safety profile in this vulnerable population.

Conclusions

The IMPULSE study showed (1) the expected pharmacodynamic response to lefitolimod, (2) positive efficacy signals in two pre-defined and clinically relevant subgroups regarding OS and (3) a favorable safety profile. This data provides significant guidance for defining patient populations most likely to benefit from treatment with lefitolimod.

Clinical trial identification

NCT02200081

Legal entity responsible for the study

Mologen AG

Funding

Mologen AG

Disclosure

M. Schmidt, M. Krikow, E. Wiegert: Employee. All other authors have declared no conflicts of interest.