TTFields combined with PD-1 inhibitors or docetaxel for 2nd line treatment of non-small cell lung cancer (NSCLC): Phase 3 LUNAR study

Abstract

Background: Tumor Treating Fields (TTFields) are a non-invasive, anti-mitotic treatment modality. TTFields disrupt the formation of the mitotic spindle, and dislocation of intracellular constituents. TTFields significantly extend the survival of newly diagnosed glioblastoma patients when combined with temozolomide. Efficacy of TTFields in NSCLC has been shown preclinically and in a phase I/II pilot study with pemetrexed where overall survival (OS) improved by>5 months vs historical controls. Trial design: We hypothesize that adding TTFields to 2nd line therapies in advanced NSCLC will increase OS. Patients (N=512) with squamous or non-squamous NSCLC are enrolled in this Phase 3 study LUNAR [NCT02973789]. Patients are stratified by 2nd line therapy (PD-1 inhibitor or docetaxel), histology (squamous vs. nonsquamous) and geographical region. Key inclusion criteria are 1st disease progression (RECIST 1.1), ECOG 0-1, no prior surgery or radiation therapy, no electronic medical devices in the upper torso, and absence of brain metastasis. Docetaxel or PD-1 inhibitors (either nivolumab or pembrolizumab) are given at standard doses. TTFields are applied to the upper torso for at least 18 hours/day, allowing patients to maintain daily activities. TTFields are continued until progression in the thorax and/or liver according to the immune-related response criteria (irRC). Follow up is performed once q6 weeks including CT scans of the chest and abdomen. On progression in the upper torso patients are followed monthly for survival. The primary endpoint is superiority in OS between patients treated with TTFields in combination with either docetaxel or PD-1 inhibitors, compared to docetaxel or PD-1 inhibitors alone. A co-primary endpoint compares the OS in patients treated with TTFields and docetaxel to those treated with PD-1 inhibitors alone in a non-inferiority analysis. Secondary endpoints include progression-free survival, radiological response rate based on the irRC, quality of life based on the EORTC QLQ C30 questionnaire and severity & frequency of adverse events. The sample size is powered to detect a HR of 0.75 in TTFields-treated patients versus control group.