By Tristan Manalac

Pictured: Magnifying glass focusing on a tumor in an ovary/iStock, Mohammed Haneefa Nizamudeen
In the Phase III INNOVATE-3 trial, Novocure’s investigational ovarian cancer therapy Tumor Treating Fields was unable to significantly improve overall survival, the company announced Monday.
Patients who received Tumor Treating Fields (TTFields) treatment combined with paclitaxel had a median overall survival (OS) of 12.2 months, which was only marginally higher than the 11.9-month median OS in comparators treated with paclitaxel alone.
In terms of safety, TTFields remained well-tolerated and showed no new signals of concerns or systemic toxicities. Its adverse event profile in INNOVATE-3 was consistent with what had previously been reported.
TTFields is an investigational oncology therapy that uses electric fields that act via many different mechanisms to kill cancer cells. Because it works via several pathways, the approach can be combined with other treatment modalities—such as PARP inhibitors and immune checkpoint inhibitors—to potentially enhance their effectiveness.
The investigational therapy also exploits the unique traits of malignant cells, such as their higher division rate and different electrical properties, in turn avoiding significant damage on healthy cells.
Novocure tested TTFields’ mechanism of action in INNOVATE-3, also dubbed ENGOT-ov50 and GOG-3029. The randomized and open-label trial enrolled 540 patients with platinum-resistant ovarian cancer. Aside from OS, the study also evaluated progression-free survival and objective response rate as secondary endpoints.
In an exploratory subgroup analysis also revealed Monday, Novocure detected a potential survival benefit in patients who had undergone only one prior line of therapy. According to the company, this signal “could merit further exploration” as a potential treatment option for the approximately 20% of ovarian cancer patients with limited response to frontline platinum treatments.
While Novocure Executive Chairman William Doyle called INNOVATE-3’s main results “disappointing,” he considered the signals of efficacy encouraging and indicative of a “potential clinical benefit when TTFields is initiated early in a patient’s treatment journey.”
NovoCure did not provide specific data in its press release Monday and is currently still completing its analyses. The company will share full results in the future.
Despite stumbling in ovarian cancer, TTFields has demonstrated its therapeutic potential in other oncology indications. In January 2023, the investigational therapy aced the Phase III LUNAR trial in non-small cell lung cancer, leading to significant and clinically meaningful improvements in OS when used in conjunction with standard of care.
In July 2023, an independent data monitoring committee recommended that the Phase III PANOVA-3 study in pancreatic cancer proceed to its final analysis.