Novocure’s Optune Mya Gets FDA Not Approvable Letter

The US Food and Drug Administration (FDA) issued a not approvable letter for its premarket approval (PMA) application for Optune Mya in adults with brain metastases from non–small cell lung cancer (NSCLC) following stereotactic radiation. The agency determined that uncertainty about the degree of clinical benefit provided by the device prevented approval. The FDA did not raise concerns about the device's safety profile.¹

Novocure, the sponsor, is evaluating the FDA's feedback and plans to meet with the agency to determine whether options are available to support approval without additional clinical studies. The company cautioned that there is no assurance these discussions or any future regulatory submissions will lead to approval.

What is Optune Mya?

Optune Mya is a wearable tumor treating fields (TTFields) device for brain metastases from NSCLC after stereotactic radiation. It delivers alternating electric fields applied through arrays placed on the scalp to disrupt cancer cell division. The PMA application was supported by findings from the phase 3 METIS trial (NCT02831959), which evaluated TTFields following stereotactic radiosurgery (SRS) in patients with brain metastases from NSCLC.²

METIS Met Its Primary End Point but Did Not Improve Overall Survival

METIS randomized 298 adults with 1 to 10 newly diagnosed brain metastases from NSCLC to receive SRS followed by TTFields at 150 kHz (n = 149) or SRS alone (n = 149). Patients with known actionable mutations, including ALK, EGFR, ROS1, or BRAF, were excluded. The primary end point was time to intracranial progression, assessed by a blinded independent radiology review committee.

The study met its primary end point, with TTFields significantly delaying time to intracranial progression compared with SRS alone (HR, 0.72; 95% CI, 0.53-0.98; Fine-Gray P = .044). This represented a 28% reduction in the risk of intracranial progression. At 12 months, intracranial progression rates were 46.9% with TTFields vs 59.4% with SRS alone (P = .023). At 24 months, the rates were 53.6% vs 65.2% (P = .031); this analysis was post hoc.²

The improvement in intracranial progression did not translate into a significant overall survival (OS) benefit. Median OS was 11.3 months with TTFields vs 10.6 months with SRS alone (HR, 1.04; log-rank P = .763). Investigators also reported no significant differences in time to neurocognitive failure or radiologic response rate. Time to neurocognitive failure, OS and radiological response rate did not differ significantly.

Time to distant intracranial progression favored TTFields but did not reach statistical significance (HR, 0.76; 95% CI, 0.51-1.12; P = .165).

In a post hoc subgroup analysis of 118 patients receiving immune checkpoint inhibitors (ICIs) for their primary disease, the association between TTFields and longer time to intracranial progression was more pronounced (HR, 0.63; 95% CI, 0.39-1.00). The Cox analysis reached nominal statistical significance (P = .049), whereas the Fine-Gray analysis did not (P = .055). TTFields were also associated with longer time to distant intracranial progression in this subgroup (HR, 0.41; 95% CI, 0.21-0.81; P = .0087).

Regarding safety, device-related adverse events occurred in 65 of 129 patients who received TTFields, primarily grade 1 or 2 skin events. Two grade 3 or greater device-related nervous system events were reported: 1 seizure and 1 case of brain edema. Seven patients (5.4%) discontinued the device because of device-related adverse events. One fatal seizure was initially considered possibly related to the device by the investigator, although a steering committee subsequently determined that it was unlikely to be related.

The investigators identified the open-label design and absence of a sham device as study limitations. They also noted that neurocognitive and quality-of-life data were incomplete and that the trial was not powered to evaluate these outcomes.

RELATED: Minesh Mehta, MD, chief of radiation oncology and deputy director at Miami Cancer Institute, part of Baptist Health South Florida discussed the phase 3 findings and the potential role of TTFields following SRS in patients with NSCLC brain metastases in a previous Targeted Onc^TM interview.

TTFields Have a Separate FDA Approval in Metastatic NSCLC

The FDA approved Novocure's Optune Lua in October 2024 for concurrent use with PD-1/PD-L1 inhibitors or docetaxel in adults with metastatic NSCLC whose disease progressed on or after a platinum-based regimen.³ The approval was supported by findings from the phase 3 LUNAR trial (NCT02973789), which evaluated TTFields plus standard systemic therapy vs standard systemic therapy alone in patients with stage 4 NSCLC following progression on or after platinum-based therapy.

In the intention-to-treat population, patients receiving TTFields plus standard systemic therapy (n = 145) had a median OS of 13.2 months (95% CI, 10.3-15.5) vs 9.9 months (95% CI, 8.2-12.2) among those receiving standard systemic therapy alone (n = 146; HR, 0.76; 95% CI, 0.58-0.99; P = .042). Standard systemic therapy consisted of either a PD-1/PD-L1 inhibitor or docetaxel.

In a prespecified secondary analysis of patients receiving PD-1/PD-L1 inhibitors, median OS was 19.0 months with the addition of TTFields vs 10.8 months with immunotherapy alone (HR, 0.63; 95% CI, 0.42-0.95; P = .026).³

What Happens Next for Optune Mya?

The not approvable letter for Optune Mya represents a separate regulatory decision involving the use of TTFields following stereotactic radiation in patients with NSCLC brain metastases. Novocure plans to continue discussions with the FDA to determine whether the application can move forward without additional clinical studies.

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 10, 2026. https://tinyurl.com/3masukf8

2. Mehta MP, Gondi V, Ahluwalia MS, 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

3. FDA summary of safety and effectiveness data: Optune Lua (PMA P230042). US Food and Drug Administration; October 15, 2024. https://www.accessdata.fda.gov/cdrh_docs/pdf23/P230042b.pdf