Limertinib Wins Approval in China for EGFR T790M+ NSCLC

China’s National Medical Products Administration (NMPA) has approved limertinib (ASK120067) for the treatment of adult patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring an EGFR T790M mutation.1

The regulatory decision was supported by data from a pivotal phase 2b trial (NCT03502850), which demonstrated that patients treated with limertinib (n = 301) achieved an overall response rate (ORR) of 68.8% (95% CI, 63.2%-74.0%) and a disease control rate (DCR) of 92.4% (95% CI, 88.8%-95.1%) per independent review committee (IRC) assessment.1,2 The median duration of response (DOR) was 11.1 months (95% CI, 9.6-13.8), and the median progression-free survival (PFS) was 11.0 months (95% CI, 9.7-12.4). The median overall survival (OS) was not reached (95% CI, 19.7 months-not evaluable [NE]).

Patients harboring central nervous system (CNS) lesions (n = 99) experienced a CNS best-ORR of 65.9% and a median PFS of 10.6 months (95% CI, 5.6-NE).1,2

The safety profile of limertinib was consistent with that of other EGFR-targeted therapies.1

“Limertinib has demonstrated significant efficacy and safety in [patients with] NSCLC with EGFR T790M mutations and EGFR-sensitive mutations. Patients treated with limertinib showed a reduced risk of CNS progression or death. This approval brings new hope and options to patients with advanced EGFR-mutated NSCLC in China,” Shi Yuankai, MD, a professor in the Department of Medical Oncology at the Chinese Academy of Medical Sciences and principal investigator of the phase 2b study, stated in a news release.

The single-arm, open-label phase 2b study enrolled patients 18 to 70 years of age with histologically or cytologically confirmed metastatic or unresectable, locally advanced, recurrent NSCLC harboring an EGFR mutation known to be associated with EGFR TKI sensitivity.3 Patients needed to have radiological documentation of disease progression following previous continuous treatment with an EGFR TKI and documented evidence of an EGFR T790M mutation after disease progression on the most recent treatment regimen.

Other key inclusion criteria consisted of an ECOG performance status of 0 to 2 and a life expectancy of at least 12 weeks. Patients were excluded if they had received a prior third-generation EGFR TKI; received any cytotoxic chemotherapy, investigational agent, or other anticancer drug within 14 days of first study treatment; or undergone major surgery within 4 weeks of the first dose of study treatment.

During the phase 2b portion of the study, all patients received limertinib at 160 mg twice per day until disease progression or unacceptable toxicity.2

IRC-assessed ORR per RECIST 1.1 criteria served as the trial’s primary end point. Secondary end points included DCR, PFS, DOR, OS, and safety.

Additional safety data showed that 96.0% of patients experienced at least 1 treatment-related adverse effect (TRAE). The most TRAEs included diarrhea (81.7%), anemia (32.6%), rash (29.9%), and anorexia (28.2%). Grade 3 or higher TRAEs were reported in 34.6% of patients, and the most common comprised diarrhea (13.0%), hypokalemia (4.3%), anemia (4.0%), and rash (3.3%). TRAEs led to dose interruption and dose discontinuation in 24.6% and 2% of patients, respectively. No TRAEs led to death.

Another new drug application seeking the approval of limertinib for the first-line treatment of patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations is currently under review by the NMPA.1,4 This application was supported by data from a phase 3 trial (NCT04143607) evaluating limertinib vs gefitinib (Iressa); this study met its PFS primary end point.

“The approval of limertinib’s first indication marks a significant milestone, providing new treatment options for [patients with EGFR] T790 mutation–positive lung cancer who have progressed after previous EGFR TKI treatments,” Hui Zhou, PhD, senior vice president of Innovent Biologics, added in a news release.1 “We anticipate the first-line treatment indication will benefit even more patients in the near future. As our 14th commercial product, limertinib represents an important advancement in precision medicine for lung cancer. We look forward to working with ASK Pharm to bring limertinib to market and benefit Chinese patients with EGFR-mutated NSCLC.”

References

• Innovent and ASK Pharm jointly announce NMPA approval of limertinib, a third-generation EGFR TKI for the treatment of lung cancer. News release. Innovent Biologics. January 17, 2025. Accessed January 17, 2025. https://www.prnewswire.com/news-releases/innovent-and-ask-pharm-jointly-announce-nmpa-approval-of-limertinib-a-third-generation-egfr-tki-for-the-treatment-of-lung-cancer-302353761.html
• Shi Y, Li B, Wu L, et al. Efficacy and safety of limertinib (ASK120067) in patients with locally advanced or metastatic EGFR Thr790Met-mutated NSCLC: a multicenter, single-arm, phase 2b study. J Thorac Oncol. 2022;17(10):1205-1215. doi:10.1016/j.jtho.2022.05.011
• Safety, tolerability, pharmacokinetics and anti-tumour activity of ASK120067 in locally advanced and metastatic non small cell lung cancer. ClinicalTrials.gov. Updated September 16, 2020. Accessed January 17, 2025. https://clinicaltrials.gov/study/NCT03502850
• ASK120067 versus gefitinib as first-line treatment for EGFRm locally advanced or metastatic NSCLC. ClinicalTrials.gov. Updated June 14, 2024. Accessed January 17, 2025. https://clinicaltrials.gov/study/NCT04143607