Abstract CT071: LUNAR - A phase 3 trial of TTFields in combination with PD-1 inhibitors or docetaxel for second line treatment of non-small cell lung cancer (NSCLC) (2017)

Abstract BACKGROUND Tumor Treating Fields (TTFields) is a novel, non-invasive, anti-mitotic treatment modality, based on low intensity alternating electric fields. TTFields predominantly affect two phases of mitosis: metaphase – by disrupting the formation of the mitotic spindle, and cytokinesis – by dielectrophoretic dislocation of intracellular constituents. TTFields were shown to significantly extend the survival of newly diagnosed glioblastoma patients when combined with temozolomide. Efficacy of TTFields in non-small cell lung cancer (NSCLC) of all histologies has been demonstrated in multiple in vitro and in vivo models as well as in a phase I/II pilot study in combination with pemetrexed, where overall survival was extended by more than five months compared to historical controls. LUNAR TRIAL DESIGN The hypothesis of the study is that the addition of TTFields to standard of care second line therapies in advanced NSCLC will increase OS compared to treatment with standard second line alone. 512 patients with either squamous or non-squamous NSCLC will be enrolled in this prospective, randomized study. Patients will be stratified based on: 1) second line therapy (either PD-1 inhibitor or docetaxel), histology (squamous Vs. non-squamous) and geographical region. The main eligibility criteria are first disease progression (per RECIST Criteria 1.1), ECOG score of 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) will be administered at the standard dose. TTFields will be applied to the upper torso using a small, portable medical device for at least 18 hours/day at home, allowing patients to maintain daily activities. TTFields will be continued until progression in the thorax and/or liver according to the immune-related response criteria (irRC). Follow up will be performed once q6 weeks, including a CT scan of the chest and abdomen. Following progression in the upper torso, patients will be followed monthly for survival. The primary endpoint will be superiority in overall survival (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 will compare 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 &amp; frequency of adverse events. The sample size is powered to detect a Hazard Ratio of 0.75 of TTFields-treated patients compare to the control group. Citation Format: Uri Weinberg, Ori Farber, Moshe Giladi, Ze'ev Bomzon, Eilon Kirson. LUNAR - A phase 3 trial of TTFields in combination with PD-1 inhibitors or docetaxel for second line treatment of non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT071. doi:10.1158/1538-7445.AM2017-CT071