Thomas, M;
Ponce-Aix, S;
Navarro, A;
Riera-Knorrenschild, J;
Schmidt, M;
Wiegert, E;
Kapp, K;
... IMPULSE study team; + view all
(2018)
Immunotherapeutic maintenance treatment with toll-like receptor 9 agonist lefitolimod in patients with extensive-stage small-cell lung cancer: Results from the exploratory, controlled, randomized, international phase 2 IMPULSE study.
Annals of Oncology
, 29
(10)
, Article mdy326. 10.1093/annonc/mdy326.
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Abstract
Background: The immune surveillance reactivator lefitolimod (MGN1703), a DNA-based TLR9 agonist, might foster innate and adaptive immune response and thus improve immune-mediated control of residual cancer disease. The IMPULSE phase 2 study evaluated the efficacy and safety of lefitolimod as maintenance treatment in extensive-stage small-cell lung cancer (ES-SCLC) after objective response to first-line chemotherapy, an indication with a high unmet medical need and stagnant treatment improvement in the last decades. Patients and methods: 103 patients with ES-SCLC and objective tumor response (as per RECIST 1.1) following 4 cycles of platinum-based first-line induction therapy were randomized to receive either lefitolimod maintenance therapy or local standard of care at a ratio of 3:2 until progression or unacceptable toxicity. Results: From 103 patients enrolled, 62 were randomized to lefitolimod, 41 to the control arm. Patient demographics and response patterns to first-line therapy were balanced. Lefitolimod exhibited a favorable safety profile and pharmacodynamic assessment confirmed the mode-of-action showing a clear activation of monocytes and production of interferon-gamma-induced protein 10 (IP-10). While in the ITT population no relevant effect of lefitolimod on progression-free and overall survival (OS) could be observed, two pre-defined patient subgroups indicated promising results, favoring lefitolimod with respect to OS: in patients with a low frequency of activated CD86+ B cells (hazard ratio, HR 0.53, 95%CI 0.26-1.08; n = 38 of 88 analyzed) and in patients with reported chronic obstructive pulmonary disease (COPD) (HR 0.48, 95%CI 0.20-1.17, n = 25 of 103). Conclusions: The IMPULSE study showed no relevant effect of lefitolimod on the main efficacy endpoint OS in the ITT, but (1) the expected pharmacodynamic response to lefitolimod, (2) positive OS efficacy signals in two pre-defined subgroups and (3) a favorable safety profile. These data support further exploration of lefitolimod in SCLC.
| Type: | Article |
|---|---|
| Title: | Immunotherapeutic maintenance treatment with toll-like receptor 9 agonist lefitolimod in patients with extensive-stage small-cell lung cancer: Results from the exploratory, controlled, randomized, international phase 2 IMPULSE study |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/annonc/mdy326 |
| Publisher version: | https://doi.org/10.1093/annonc/mdy326 |
| Language: | English |
| Additional information: | This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
| Keywords: | SCLC, lefitolimod, TLR9 agonist, immunotherapy |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10054944 |
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