Topline Phase 3 TRIDENT Results Evaluate Early TTFields Therapy Initiation in Newly Diagnosed Glioblastoma – Novocure

Novocure announced topline results from its Phase 3 TRIDENT trial, which evaluated the initiation of Tumor Treating Fields (TTFields) therapy for newly diagnosed glioblastoma (GBM) at the start of chemoradiation (Early Start Arm) compared to initiating TTFields therapy during the subsequent maintenance phase of treatment (Maintenance Start Arm).

The trial did not demonstrate a statistically significant improvement in the primary endpoint of overall survival for the Early Start Arm compared to the Maintenance Start Arm. In the intent-to-treat (ITT) population, the Early Start Arm had a median overall survival of 17.7 months compared to 17.5 months in the Maintenance Start Arm (HR 0.953; p=0.519).

“TRIDENT represents the largest glioblastoma trial focused on optimizing the integration of Tumor Treating Fields therapy into standard chemoradiotherapy. Although the study did not meet its primary endpoint, it reaffirmed the clinical value of Tumor Treating Fields therapy and demonstrated promising signals that earlier initiation of TTFields treatment may improve outcomes for selected patients.” – Wenyin Shi, MD, PhD, Professor of Radiation Oncology, Co-Director of the Jefferson Brain Tumor Center at Sidney Kimmel Comprehensive Cancer Center, Thomas Jefferson University.

The survival results in the ITT population in both study arms were durable over a long-term period with the one-, two-, and three-year survival rates in the Early Start Arm achieving 70.9%, 33.9% and 22.5%, respectively. In the Maintenance Start Arm, the survival rates were 72.0%, 31.6% and 18.4%, respectively.

TRIDENT enrolled 981 patients who were randomized shortly after surgery, including those who experienced clinical or radiographic deterioration during chemoradiation therapy. Approximately 25% of patients did not initiate the maintenance phase across both arms of the trial. The median patient age was 60 years. Baseline characteristics of the patient population were balanced across both arms of the trial and included: 38% of patients with a KPS of 70 or 80; 39% with a methylated MGMT promoter and 5% had IDH-mutant tumors. The extent of surgical resection was also balanced across arms, 51% of patients had a gross total resection, 37% a partial resection, and 12% biopsy only.

“We are committed to improving the treatment of glioblastoma and are grateful to our investigators and the patients and families who made the TRIDENT trial possible. The study did not meet its primary endpoint, but the results from TRIDENT demonstrated the feasibility and safety of initiating Tumor Treating Fields therapy during chemoradiation. We look forward to sharing additional analyses from this trial, which may inform future treatment approaches for patients with specific characteristics.” – Uri Weinberg, MD, PhD, Chief Medical and Innovation Officer, Novocure.

TTFields therapy, including initiation with chemoradiation, was well-tolerated, and did not lead to any new safety signals. Device related safety was consistent with prior clinical studies of TTFields therapy in GBM.