Novocure’s Phase 3 TRIDENT Trial Misses Survival Endpoint in Glioblastoma, Confirms Safety of Early TTFields Use

Novocure has reported topline results from the Phase 3 TRIDENT trial evaluating whether initiating Tumor Treating Fields (TTFields) therapy during chemoradiation could improve outcomes for patients with newly diagnosed glioblastoma (GBM). The study did not meet its primary endpoint, showing no statistically significant improvement in overall survival compared with initiating TTFields during the maintenance phase after chemoradiation.

In the intent-to-treat population, patients who started TTFields alongside chemoradiation achieved a median overall survival of 17.7 months, compared with 17.5 months for those who began treatment during maintenance therapy (HR 0.953; p=0.519).

TTFields and the Need for Better Glioblastoma Treatments

Glioblastoma remains the most common and aggressive primary malignant brain tumor in adults. Despite surgery, radiation therapy, and temozolomide chemotherapy, most patients experience disease progression, and long-term survival remains limited.

TTFields therapy uses low-intensity alternating electric fields delivered through wearable transducer arrays placed on the scalp. These electric fields disrupt cancer cell division through multiple mechanisms, leading to tumor cell death while largely sparing healthy cells. TTFields therapy is already part of standard treatment for newly diagnosed glioblastoma in several regions worldwide.

TRIDENT Trial Results

TRIDENT (NCT00916409) was a global Phase 3, randomized, open-label study that enrolled 981 patients shortly after surgery. Participants were assigned to receive TTFields either at the start of chemoradiation (Early Start Arm) or after completion of chemoradiation during the maintenance phase (Maintenance Start Arm).

The study represented the largest glioblastoma trial focused on optimizing the timing of TTFields integration into standard treatment.

Although the primary endpoint was not met, survival outcomes remained durable in both treatment groups. In the Early Start Arm, one-, two-, and three-year survival rates were 70.9%, 33.9%, and 22.5%, respectively. Corresponding rates in the Maintenance Start Arm were 72.0%, 31.6%, and 18.4%.

Baseline characteristics were balanced across treatment arms. The median patient age was 60 years, while 39% of patients had methylated MGMT promoters and 5% had IDH-mutant tumors. Surgical outcomes were also comparable, with 51% undergoing gross total resection, 37% partial resection, and 12% biopsy only.

Approximately one-quarter of enrolled patients did not reach the maintenance treatment phase, reflecting the aggressive nature of glioblastoma and the challenges associated with disease progression during initial therapy.

Safety Findings Support Earlier Use

TTFields therapy initiated during chemoradiation demonstrated a safety profile consistent with previous studies. Investigators reported no new safety signals, and treatment remained well tolerated throughout the study.

According to lead investigator Dr. Wenyin Shi of Thomas Jefferson University, the findings reinforce the clinical value of TTFields therapy while suggesting that earlier treatment initiation may still offer benefits for selected patient populations. Novocure’s Chief Medical and Innovation Officer, Dr. Uri Weinberg, noted that additional analyses are underway to identify patient subgroups that could derive greater benefit from early treatment initiation.

Path Forward

While TRIDENT did not establish a survival advantage for earlier TTFields initiation in the overall study population, the trial confirmed that concurrent use with chemoradiation is feasible and safe. Novocure plans to present the full dataset at the American Society for Radiation Oncology (ASTRO) 2026 Annual Meeting, where subgroup analyses and secondary endpoint findings may provide further insight into optimizing TTFields treatment strategies for patients with glioblastoma.

What Do the TRIDENT Results Mean for Patients?

The TRIDENT trial does not alter the established role of Tumor Treating Fields (TTFields) in newly diagnosed glioblastoma, as it compared treatment timing rather than TTFields versus standard care. Starting TTFields earlier during chemoradiation did not significantly extend survival, but both groups achieved durable outcomes. The study confirms TTFields can be safely combined with chemoradiation, giving physicians flexibility to tailor initiation based on patient needs. Ongoing analyses may reveal subgroups more likely to benefit from earlier use, supporting a more personalized approach to care.

Reference

Novocure Announces Topline Data from the Phase 3 TRIDENT Trial Evaluating Earlier Use of Tumor Treating Fields Therapy in Newly Diagnosed Glioblastoma | Thu, 06/18/2026 – 07:00