FDA Accepts PMA Application Seeking Approval of TTFields Therapy in NSCLC for Filing

FDA

A premarket approval (PMA) application regarding the addition of tumor-treating fields (TTFields) to standard-of-care (SOC) therapies in patients with non­–small cell lung cancer (NSCLC) after disease progression on or following platinum-based treatment has been accepted for filing by the FDA.¹

The PMA was supported by data from the phase 3 LUNAR study (NCT02973789) in which TTFields therapy paired with standard therapeutic options (n = 137) resulted in a median overall survival (OS) of 13.2 months (95% CI, 10.3-15.5) vs 9.9 months (95% CI, 8.1-11.5) with SOC therapies alone (n = 139), translating to a 26% reduction in the risk of death in the intention-to-treat (ITT) population (HR, 0.74; 95% CI, 0.56-0.98; P = .035).2 In the TTFields/SOC arm, the 1- and 3-year survival rates were 53% (95% CI, 44%-61%) and 18% (95% CI, 11%-27%), respectively; in the SOC-only arm, these rates were 42% (95% CI, 34%-50%) and 7% (95% CI, 2%-15%), respectively.

Those who received TTFields therapy combined with physician’s choice of immune checkpoint inhibition (ICI; n = 66) experienced a median OS of 18.5 months (95% CI, 10.6-30.3) vs 10.8 months (95% CI, 8.2-18.4) in those given ICI alone (n = 68), translating to a 37% reduction in the risk of death (HR, 0.63; 95% CI, 0.41-0.96; P = .03). In the TTFields/ICI arm, the 1- and 3-year survival rates were 60% (95% CI, 47%-71%) and 27% (95% CI, 15%-42%), respectively; in the ICI-alone arm, these rates were 46% (95% CI, 33%-57%) and 9% (95% CI, 3%-21%), respectively.

Moreover, a positive survival trend was observed in those who received TTFields plus docetaxel (n = 71) vs those given docetaxel alone (n = 71), at 11.1 months (95% CI, 8.2-14.1) and 8.7 months (95% CI, 6.3-11.3), respectively (HR, 0.81; 95% CI, 0.55-1.19; P = .28). The 1-yr survival rates in the TTFields/docetaxel arm were 46% (95% CI, 33%-57%) vs 38% (95% CI, 27%- 49%) in the docetaxel-alone arm; the respective 3-year survival rates were 9% (95% CI, 3%-20%) and 5% (95% CI, 0%-18%).

“We are thrilled to announce the FDA has accepted our PMA application for review of the LUNAR data in NSCLC,” Asaf Danziger, chief executive officer of Novocure, stated in a press release.¹ “This significant milestone brings us one step closer to treating patients seeking treatment for NSCLC, post-platinum, for which very few effective non-toxic options exist today. I would like to thank our investigators and patients, as well as our Novocure colleagues, for their dedication in pursuit of bringing our novel therapy to thousands of patients in need.”

TTFields are electric fields that employ physical forces on electrically charged components in dividing cancer cells to produce an antimitotic effect.² Downstream effects comprise cell stress–induced immunogenic cell death and prompting antitumor responses in the immune system. The therapy is locoregionally administered to the chest through a wearable medical device and adhesive bandages with hydrogel-covered biocompatible insulated ceramic discs.

The study enrolled patients with metastatic NSCLC who were 22 years of age or older and who had experienced disease progression on or following platinum-based treatment. Patients were required to have an ECOG performance status ranging from 0 to 2.

After undergoing a baseline examination, which included an MRI, patients (n = 276) were randomly assigned 1:1 to receive TTFields therapy at 150 kHz for at least 18 hours per day plus SOC defined as investigator’s choice of ICI or docetaxel or SOC alone. Those given ICIs could have received pembrolizumab (Keytruda), nivolumab (Opdivo), or atezolizumab (Tecentriq). Randomization was stratified by region, SOC treatment, and disease histology.

OS served as the trial’s primary end points, and key secondary end points include OS in the ICI- and docetaxel-treated subgroups. Other end points of interest comprise progression-free survival (PFS), overall response rate (ORR), PFS and OS by histology, quality of life, and safety.

Data presented at the 2023 ASCO Annual Meeting had a data cutoff date of November 26, 2022. Baseline demographics were comparable across the treatment arms. In the overall population, the median age was 64 years (range, 22-86) and most patients were male (65%), White (80%), and had an ECOG performance status of 1 (68%). Regarding region, 30% of patients were from North America, 30% were from Western Europe and Israel, 30% were from Eastern Europe, and 9% were from East Asia. Most patients (84%) were current or former smokers.

In terms of histology, 56% of patients had nonsquamous disease and the remaining 44% had squamous disease. Eighty-nine percent of patients previously received 1 line of systemic treatment and 11% received 2 or more prior lines. Thirty-one percent of patients had prior exposure to an ICI. The best response to any prior treatment was complete response (CR) for 5% of patients, partial response (PR) for 25%, stable disease (SD) for 33%, and disease progression (PD) for 14%; this information was unknown for 14% of patients. Sixteen percent of patients had liver metastasis and 1% had central nervous system metastasis.

When broken down by subgroups, the median OS in those with nonsquamous disease who received TTFields paired with SOC (n = 79) was 12.6 months (95% C, 8.8-19.8) vs 9.9 months (95% CI, 6.9-16.4) in those who were given SOC (n = 77; HR, 0.80; 95% CI, 0.54-1.16; P = .28). In the squamous subgroup, those given TTFields/SOC (n = 58) experienced a median OS of 13.9 months (95% CI, 9.7-17.1) vs 10.1 months (95% CI, 8.3-14.3) in those given SOC alone (n = 62; HR, 0.67; 95% CI, 0.44-1.01; P = .05).

In the ITT population, the median PFS with TTFields plus SOC vs SOC alone was 4.8 months (95% CI, 4.1-5.7) vs 4.1 months (95% CI, 3.1-4.6), respectively (HR, 0.85; 95% CI, 0.67-1.11; P =.23).

TTFields plus SOC elicited an ORR of 20% (95% CI, 14%-28%) vs 17% (95% CI, 11%-25%) with SOC alone, translating to a percentage difference of 3% (P = .5). In the TTFields/SOC arm, best overall responses included CR (3%), PR (18%), SD (49%), and PD (18%); 2% of patients were not response evaluable. Notably, all 5 CRs were experienced by those receiving an ICI (n = 4 with TTFields therapy; n = 1 with ICI alone).

Any-grade adverse effects (AEs) occurred in 97% of those in the TTFields/SOC arm vs 91% of those in the SOC-alone arm; these effects were grade 3 or higher in 59% and 56% of patients, respectively. There was a comparable incidence of grade 3 or higher AEs between the treatment arms. The most common grade 3 or higher AEs in the TTFields/SOC and SOC-alone arms, respectively, included leukopenia (14% vs 14%), pneumonia (11% vs 11%), anemia (8% vs 8%), dyspnea (7% vs 3%), fatigue (4% vs 8%), musculoskeletal pain (3% vs 4%), respiratory tract infection (3% vs 0%), dermatitis (2% vs 0%), diarrhea (2% vs 0%), localized edema (1% vs 2%), cough (0% vs 1%), nausea (0% vs 1%), and alopecia (0% vs 1%).

Serious AEs were experienced by 53% of those in the TTFields/SOC arm vs 38% of those in the SOC-alone arm. AEs led to treatment discontinuation for 36% vs 20% of patients, respectively; AEs resulted in death for 10% and 8% of patients, respectively.

References

1. Novocure announces FDA acceptance of the PMA application for TTFields therapy in non-small cell lung cancer. News release. Novocure. January 18, 2024. Accessed January 18, 2024. https://www.novocure.com/novocure-announces-fda-acceptance-of-the-pma-application-for-ttfields-therapy-in-non-small-cell-lung-cancer/
2. Leal T, Kotecha R, Ramlau R, et al. Tumor treating field (TTFields) therapy with standard of care (SOC) in metastatic non-small cell lung cancer (mNSCLC) following platinum failure randomized, phase 3 LUNAR study. J Clin Oncol. 2023;41(suppl 17):LBA9005. doi:10.1200/JCO.2023.41.17_suppl.LBA9005