TRIDENT PHASE 3 TRIAL (EF-32): FIRST-LINE TUMOR TREATING FIELDS (TTFIELDS; 200 KHZ) CONCOMITANT WITH CHEMO-RADIATION, FOLLOWED BY MAINTENANCE TTFIELDS/TEMOZOLOMIDE IN NEWLY-DIAGNOSED GLIOBLASTOMA

Abstract INTRODUCTION Tumor Treating Fields (TTFields; 200 kHz; non-invasive, loco-regional antimitotic treatment) is approved for newly-diagnosed glioblastoma (ndGBM). In the Phase 3 EF-14 trial, post-surgical radiotherapy/temozolomide, followed by maintenance TTFields/temozolomide significantly increased overall survival (OS) and progression-free survival (PFS) in patients with ndGBM versus TMZ alone. Addition of maintenance TTFields did not increase systemic toxicity; and related adverse events (AEs) were mainly dermatological. In preclinical models, addition of TTFields increased the benefit of radiotherapy. Two pilot studies showed that TTFields concomitant with radiotherapy/temozolomide is feasible and well-tolerated. The benefit of TTFields concomitant with radiotherapy/temozolomide will be investigated in the TRIDENT trial. METHODS TRIDENT (EF-32; NCT04471844) is an international, pivotal, phase 3 randomized trial comparing triple-combination of TTFields/radiotherapy/temozolomide versus standard radiotherapy/temozolomide. Patients in both arms will receive maintenance TTFields/TMZ. Arrays of the Optune® System will be used to deliver TTFields (200 KHz) for ≥18 hours/day concomitant with radiotherapy. TTFields treatment will be continued until second disease progression (RANO) or 24 months, whichever occurs first. Patients with pathologically-confirmed ndGBM, ≥ 18 years of age (≥ 22 years of age; US), KPS ≥ 70, post-surgery/biopsy, and amenable for radiotherapy/temozolomide will be stratified by extent-of-resection and MGMT promoter methylation status. The primary endpoint is median OS. Secondary endpoints include median PFS (RANO), 1-year and 2-year survival rates, overall radiological response (ORR; RANO), PFS (PFS-6M, PFS-12M, PFS-2Y), severity and frequency of AEs (CTCAE V5.0), pathological post-treatment changes in resected GBM tumors, quality-of-life (EORTC QLQ-C30), and OS correlation to TTFields duration-of-usage. The hypothesis is that first-line TTFields/RT/TMZ triple-combination will significantly improve OS compared to radiotherapy/temozolomide; each followed by maintenance TTFields/temozolomide. Sample size (N=950; 475/arm) was powered for a HR < 0.8 with 5% type I error. Survival will be measured from time-of-randomization. The TRIDENT trial is currently enrolling patients. RESULTS/CONCLUSIONS N/A TiP.