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