Tumor treating fields concurrent with standard of care for stage 4 non-small cell lung cancer (NSCLC) following platinum failure: Phase III LUNAR study

Abstract

Background: Tumor Treating Fields (TTFields) is a non-invasive, anti-mitotic treatment approved for glioblastoma based on significantly improved survival outcomes in a Phase 3 trial. Efficacy of TTFields in NSCLC has been shown preclinically and the safety confirmed in a phase I/II pilot study combined with pemetrexed. We hypothesize that adding TTFields to immune checkpoint inhibitors or docetaxel following platinum doublet failure will increase overall survival (OS) in stage 4 NSCLC. Trial design: The LUNAR trial [NCT02973789] is enrolling patients (N=534), with squamous or non-squamous NSCLCwho are stratified per selected standard therapy (immune checkpoint inhibitors or docetaxel), histology (squamous vs. non-squamous) and geographical region. Key inclusion criteria include disease progression while on/after platinum- based therapy, ECOG0-2, no electronicmedical devices in the upper torso, and absence of brain metastasis.Docetaxel or immune checkpoint inhibitors are given at standard doses. TTFields are applied to the upper torso for>18 hours/day, allowing patients to maintain daily activities. TTFields are continued until progression in the thorax and/or liver. Follow-up is performed once q6weeks usingCT scans of the chest and abdomen.On progression in the thorax and/or liver, patients have 3 post-progression follow-up visits and are then followedmonthly for survival. The primary endpoint is superiority in OS with TTFields in combination with the standard of care treatments versus (vs) standard of care treatments alone. Key secondary endpoints compare the OS in patients treated with TTFields and docetaxel vs docetaxel alone, and patients treated with TTFields and immune checkpoint inhibitors vs those treated with immune checkpoint inhibitors alone. An exploratory analysiswill test non-inferiority of TTFields with docetaxel compared to checkpoint inhibitors alone. Secondary endpoints include progression-free survival, radiological response rate, quality of life based on the EORTCQLQC30 questionnaire and severity and frequency of adverse events. The sample size is powered to detect aHR of 0.75 in TTFieldstreated patients versus control group.