Phase 3 TRIDENT study (EF-32): Tumor treating fields (TTFields; 200 kHz) concomitant with chemoradiation, and maintenance TTFields therapy/temozolomide in newly diagnosed glioblastoma

TPS2083 Background: Tumor Treating Fields (TTFields) therapy, a noninvasive and locoregional antimitotic cancer treatment modality, is approved for newly diagnosed (nd), recurrent glioblastoma (r) GBM and mesothelioma. In patients with ndGBM, progression-free survival (PFS) and overall survival (OS) were significantly improved with TTFields therapy/temozolomide (TMZ) vs TMZ alone in the pivotal EF-14 study, leading to FDA approval in ndGBM. To avoid potential impedance of radiotherapy (RT), TTFields therapy was administered following RT/TMZ; however, preclinical studies have demonstrated that TTFields therapy enhances the therapeutic effect of RT. Methods: TRIDENT (EF-32; NCT04471844), a phase 3, global, randomized study, will evaluate TTFields therapy concomitant with RT/TMZ in patients ≥18 years of age (≥22 years in the US) with histologically-confirmed ndGBM, ≥3 months life expectancy, and ≥70 Karnofsky performance status. Patients will be stratified on the basis of MGMT promoter methylation status and extent of resections. Approximately 950 patients will be assigned 1:1 to continuous TTFields therapy (200 KHz, ≥18 h/day) concomitant with RT/TMZ (experimental arm) or RT/TMZ alone (control arm). Patients in the experimental arm will receive TTFields therapy continuously from the first day of chemoradiation. Patients in the control group will begin TTFields at the same time as maintenance TMZ, approximately one month after completion of chemoradiation. TTFields therapy will continue in both treatment groups until second disease progression (PFS2) or 24 months (if clinically able). The primary endpoint is median OS, and secondary endpoints include PFS, 1- and 2-year survival rates, objective response rate, PFS2, 6- and 12-month PFS rates, safety, and quality of life (EORTC QoL questionnaires). The ability of TTFields therapy to extend OS in a dose-dependent manner is an exploratory endpoint. The sample size is powered for a hazard ratio of < 0.8 with a 5% type I error. The hypothesis that first-line TTFields therapy/RT/TMZ can significantly improve OS vs RT/TMZ will be tested using a stratified log-rank test. The study is expected to enroll patients at 150 sites, with enrollment currently open in 9 countries. Clinical trial information: NCT04471844 .