September 24, 2026
Firmonertinib (Ivesa; formerly furmonertinib) elicited at a once-daily dose of 160 mg elicited intracranial responses and disease control in patients with EGFR-mutated non–small cell lung cancer (NSCLC) and leptomeningeal metastases (LM), according to data from a prospective phase 2 study presented at the International Association for the Study of Lung Cancer 2026 World Conference on Lung Cancer.¹
Among all enrolled patients (n = 26), the intracranial objective response rate (ORR) was 57.7%, consisting entirely of partial responses, and the intracranial disease control rate (DCR) was 76.9%. The median intracranial progression-free survival (iPFS) reached 19.7 months (95% CI, 15.8-not reached), with events reported in 23.0% of patients. The 12- and 18-month iPFS rates were 85.8% and 64.3%, respectively. Moreover, the median progression-free survival (PFS) was also 19.7 months (95% CI, 5.4-24.3), with events in 42.3% of patients. The 12- and 18-month PFS rates were 65.6% and 52.5%, respectively.
“Firmonertinib 160 mg demonstrated encouraging efficacy in EGFR-mutated NSCLC with leptomeningeal metastases, with particularly prolonged iPFS/PFS observed in treatment-naive patients, and was well tolerated,” Yuehong Wang, MD, of The First Affiliated Hospital, Zhejiang University School of Medicine, in Hangzhou, China, said in a presentation of the data.
Why evaluate high-dose firmonertinib in EGFR-mutated NSCLC with leptomeningeal spread?
High-dose firmonertinib was examined because LM carries a poor prognosis in NSCLC and prospective data on dose-intensified EGFR TKIs in this setting remain sparse. Left untreated, patients with NSCLC and LM have a median overall survival (OS) of just 4 to 6 weeks, and LM develops more often in EGFR-mutated disease than in EGFR wild-type disease (9.4% vs 1.7%). Third-generation EGFR TKIs have activity in the brain, and firmonertinib is a third-generation agent capable of crossing the blood-brain barrier. Firmonertinib at a dose of 160 mg was previously studied as frontline treatment for patients with untreated EGFR-mutated NSCLC with brain or leptomeningeal involvement in the phase 2 FORCE trial (NCT05379803).²
How was the phase 2 study of firmonertinib given at 160 mg in EGFR-mutated NSCLC designed?
The phase 2 study of firmonertinib 160 mg enrolled patients with confirmed LM and a sensitizing EGFR mutation, which included exon 19 deletion, L858R, G719X, S768I, or L861Q).1 Patients had an Eastern Cooperative Oncology Group (ECOG) performance status ranging from 0 to 3. Eligible patients could be treatment naive, could have developed LM after a first- or second-generation EGFR TKI, or could have developed LM after a standard-dose third-generation TKI while extracranial disease remained stable. Firmonertinib was given once daily at 160 mg until disease progression, intolerable toxicity, or withdrawal of consent.
The primary end points of the study were iPFS and PFS; secondary end points included intracranial ORR, overall survival (OS), and safety. Extracranial disease was assessed by RECIST v1.1 and intracranial disease by Response Assessment in Neuro-Oncology for Leptomeningeal Disease criteria, first at 4 weeks and then every 6 to 8 weeks. Of a planned 30 patients, 26 enrolled between April 15, 2022, and December 11, 2025; the data cutoff date for the analysis was December 22, 2025.
The median patient age was 61.5 years (range, 45-79); 76.9% were female, and 84.6% had never smoked. ECOG performance status was 1 in 42.3% of patients, 2 in 23.1%, and 3 or higher in 34.6%. The EGFR alteration was an exon 19 deletion in 53.8% of patients, L858R in 34.6%, G719X in 3.9%, and a compound mutation in 7.7%. Overall, 23.0% had received no prior systemic therapy, 38.5% had received 1 line, and 38.5% had received 2 or more lines. Moreover, 53.8% of patients had previously received a third-generation EGFR TKI.
What other efficacy outcomes did firmonertinib given at 160 mg show in EGFR-mutated NSCLC?
Outside the central nervous system, firmonertinib 160 mg produced a systemic ORR of 19.2% and a systemic DCR of 80.8%. Systemic stable disease (SD) occurred in 61.5% of patients, no patients had systemic progression, and 19.2% of patients were not evaluable (NE). Intracranially, 19.2% of patients had SD, 7.7% experienced progression, and 15.4% were NE.
PFS differed by line of therapy. Patients treated in the first line (n = 6) had a median PFS of 23.6 months (95% CI, 17.2-29.9) vs 5.4 months (95% CI, 1.3-9.5) for those treated in the second line or later (n = 20; HR, 0.022; P = .054). Those treated in the first line experienced an iPFS of 19.7 months (95% CI, 12.2-27.2) vs not reached (NR; 95% CI, NR-NR) for those treated in the second line or later (n = 20; HR, 0.029; P = .280).
Cerebrospinal fluid (CSF) cytology was available at baseline and week 4 for 20 patients. In an exploratory analysis, patients whose CSF cytology converted to negative (n = 6) had an intracranial ORR of 100%, compared with 64.3% for patients whose CSF remained positive (n = 14).
What is the safety profile of firmonertinib 160 mg in EGFR-mutated NSCLC?
Firmonertinib administered at 160 mg was associated with low-grade toxicity; no grade 3 or higher treatment-related adverse effects (TRAEs) were reported. The most frequent any-grade TRAE was decreased appetite (15.4%), followed by oral ulceration, diarrhea, leukopenia, and anemia (11.5% each), and rash and thrombocytopenia (3.8% each). No patients had serious adverse effects, died of treatment-related causes, or required a dose reduction or discontinuation. The toxicity pattern matched what has been reported previously with firmonertinib.
“Given the small sample size and heterogenous population, further studies are warranted to validate these findings,” Wang concluded.
References
- Wang YH, Fang S, Lu S, et al. Furmonertinib 160 mg for EGFR-mutated NSCLC with leptomeningeal metastases: a prospective multicenter single-arm phase II study. Presented at: International Association for the Study of Lung Cancer 2026 World Conference on Lung Cancer; September 12-15, 2026; Seoul, Republic of Korea. Abstract MO12.07.
- Yan H, Jiang W, Xiong Y, et al. High-dose furmonertinib as first-line treatment for untreated EGFR-mutated advanced NSCLC with central nervous system metastases: a phase 2 trial. Cell Rep Med. 2026;7(7):102904. doi:10.1016/j.xcrm.2026.102904
