FDA Rejects Application for TTFields in Brain Metastases From NSCLC

Novocure has received a Not Approvable Letter from the FDA in response to its premarket approval (PMA) application for Optune Mya® for the treatment of adult patients with brain metastases from non–small cell lung cancer (NSCLC) following stereotactic radiation, the company announced.¹ Optune Mya delivers Tumor Treating Fields (TTFields) therapy, which uses alternating electric fields to disrupt cancer cell division.

What did the FDA decision entail?

The Not Approvable Letter indicates that the FDA determined uncertainty around the degree of clinical benefit provided by Optune Mya, which prevented approval of the PMA application. According to the developers, the FDA did not raise concerns related to the safety profile of Optune Mya.

The company stated that it is evaluating the agency’s feedback and plans to meet with the FDA to determine whether there are any options that would support approval of the PMA application without requiring additional clinical studies, while noting that there can be no assurance that these discussions or any future submissions will lead to an approval.

What data support TTFields in NSCLC?

Previously, the pivotal phase 3 METIS trial (NCT02831959) evaluated TTFields therapy after stereotactic radiosurgery (SRS) in patients with brain metastases from NSCLC.² METIS met its primary end point; among 298 patients randomly assigned to TTFields therapy plus best supportive care (BSC) or BSC alone following SRS, TTFields therapy reduced the risk of intracranial progression (HR, 0.72; 95% CI, 0.53-0.98; P = .044). However, no significant differences were observed in the secondary end points of overall survival, time to neurocognitive failure, or radiological response, and time to distant intracranial progression trended in favor of TTFields therapy without reaching significance (HR, 0.76; 95% CI, 0.51-1.12; P = .165).

In a post hoc analysis of patients who received immune checkpoint inhibitors for their primary disease, the benefit in time to intracranial progression was more pronounced (HR, 0.63; 95% CI, 0.39-1.0; Fine-Gray P = .055; Cox P = .049). TTFields therapy did not cause an overall deterioration in quality of life, and grade 1/2 skin events were the most common device-related adverse events.

How was METIS designed?

In the phase 3 METIS trial, adults with 1 to 10 newly diagnosed NSCLC brain metastases suitable for SRS were randomly assigned 1:1 to receive SRS followed by TTFields at 150 kHz or SRS alone. Investigators determined radiologic progression based on independent radiology review committee evaluation.

The trial’s primary end point was time to intracranial progression per Response Assessment in Neuro-Oncology Brain Metastases criteria. Secondary end points included overall survival, neurocognitive function, quality of life, and safety.

Patients 18 years and older with a life expectancy of at least 3 months, a Karnofsky performance status of at least 70, and newly diagnosed brain metastases from a histologically or cytologically confirmed primary or metastatic NSCLC tumor within 5 years before the study were eligible for enrollment. Those with known somatic tumor mutations, significant edema, leptomeningeal metastases, or significant comorbidities were ineligible for study entry.

What is Optune Mya?

Optune Mya is a wearable medical device that delivers TTFields therapy, which consists of low-intensity, alternating electric fields tuned to specific frequencies that are designed to disrupt mitosis in dividing tumor cells while sparing healthy cells. Novocure’s TTFields-based products are already approved in certain countries for adults with glioblastoma, pancreatic cancer, NSCLC, malignant pleural mesothelioma, and pleural mesothelioma. The company has additional ongoing or completed trials of TTFields therapy in glioblastoma, NSCLC, and pancreatic cancer.

What are the next steps?

Novocure indicated that it is reviewing the FDA’s feedback and intends to pursue a meeting with the agency to explore potential paths to approval that would not require additional clinical studies. The company cautioned that no assurance can be given that these efforts will result in approval of the PMA application for Optune Mya in brain metastases from NSCLC.

References

1. Novocure provides regulatory update on U.S. FDA premarket approval application for Optune Mya for brain metastases from non-small cell lung cancer. News release. Novocure. November 9, 2026. Accessed November 9, 2026. https://tinyurl.com/dv25rb5b
2. Mehta MP, Gondi V, Ahluwalia M, et al. Tumor treating fields therapy after stereotactic radiosurgery for brain metastases from non-small cell lung cancer: final results of the phase 3 METIS study. Int J Radiat Oncol Biol Phys. 2026;124(2):278-293. doi:10.1016/j.ijrobp.2025.08.066