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

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%/ < 3.5%) between treatment and control arms was 41/20 and 26/15, for NSE levels (>20/≦20) 11/50 and 8/33, respectively. The figures show that patients have been adequately distributed and balanced between the two treatment arms.