WCLC 2025 - Posters & ePosters-P3.12.01 Phase II Trial of First-Line Double-Dose Firmonertinib in Locally Advanced or Metastatic NSCLC With EGFR L858R (FIRM Study)

P3.12.01 Phase II Trial of First-Line Double-Dose Firmonertinib in Locally Advanced or Metastatic NSCLC With EGFR L858R (FIRM Study)

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The updated results from the FIRM phase II study investigated double-dose firmonertinib (160 mg daily) as a first-line treatment in 33 patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring the EGFR L858R mutation. All patients had good performance status (ECOG 0-1) and no prior systemic therapy.<br /><br />With a median follow-up of 18.1 months, the study demonstrated promising efficacy. The median progression-free survival (PFS) was 21.1 months, with an 18-month PFS rate of 59.7%. The objective response rate (ORR) was 75.8%, and the disease control rate (DCR) reached 90.9%. Median overall survival (OS) was not reached, but the 12-month OS rate was high at 96.6%. These outcomes suggest significant clinical benefit over historical data for EGFR L858R-mutant NSCLC.<br /><br />The safety profile was acceptable, with 90.9% experiencing any treatment-emergent adverse events (TEAEs), mostly grade 1-2. Common TEAEs included lymphopenia, increased creatine phosphokinase, diarrhea, and creatinine elevation. Only 6.1% had grade 3 events (anemia, hyponatremia). No dose reductions, treatment discontinuations, or deaths related to treatment were reported.<br /><br />An exploratory analysis on circulating tumor DNA (ctDNA) from 28 patients showed that ctDNA detection dropped from 92.9% at baseline to 32.0% at cycle 3 day 1 (C3D1), indicating molecular response. Patients with ctDNA clearance at C3D1 had significantly longer PFS (21.1 vs. 10.7 months). Baseline ctDNA levels predicted ctDNA clearance with reasonable accuracy, supporting ctDNA as a biomarker for monitoring treatment response and guiding precision therapy.<br /><br />In conclusion, double-dose firmonertinib demonstrates effective and well-tolerated first-line treatment for EGFR L858R-mutant NSCLC. The study highlights the clinical utility of ctDNA dynamics in treatment monitoring and patient stratification. This regimen offers a promising option to improve outcomes in this patient population.

Asset Subtitle

Meiqi Shi

Meta Tag

Speaker Meiqi Shi

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

firmonertinib

double-dose

first-line treatment

EGFR L858R mutation

non-small cell lung cancer

progression-free survival

objective response rate

circulating tumor DNA

treatment-emergent adverse events

molecular response