WCLC 2025 - Posters & ePosters-EP.12.41 FUTURE Trial:First-Stage Data of Initial Firmonertinib 160mg in EGFR+/PD-L1+ Locally Advanced or Metastatic NSCLC (Simon’s Two-Stage Design)

EP.12.41 FUTURE Trial:First-Stage Data of Initial Firmonertinib 160mg in EGFR+/PD-L1+ Locally Advanced or Metastatic NSCLC (Simon’s Two-Stage Design)

Back to course

Pdf Summary

The FUTURE trial is a phase 1 Simon’s two-stage study evaluating firmonertinib, a novel irreversible third-generation EGFR tyrosine kinase inhibitor (TKI), at 160 mg daily in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or L858R mutations and concomitant positive PD-L1 expression. The study addresses an unmet need, as high PD-L1 expression in EGFR-mutant NSCLC is linked to poorer responses to EGFR TKIs. The trial enrolled 30 patients in stage 1, median age 59 years, with a balanced PD-L1 status (50% high expression, TPS≥50%; 50% low), and notable 27% had brain metastases.<br /><br />The primary endpoint was a 1-year progression-free survival (PFS) rate. Results demonstrated a promising 73.3% 1-year PFS rate, surpassing the 60% target for stage 1 success. The investigator-assessed overall response rate (ORR) was 86.7%, with disease control rate (DCR) at 96.7%. Subgroup analysis revealed an ORR of 100% in the low PD-L1 expression group and 73.3% in high PD-L1 expression. Mean tumor shrinkage was 56%. The safety profile was favorable: 40% experienced treatment-related adverse events (TRAEs), with only 6.7% grade 3 TRAEs including elevated liver enzymes and paronychia; most side effects were manageable and mild to moderate in severity.<br /><br />These early data suggest firmonertinib 160 mg yields robust and durable clinical benefit with manageable toxicity in first-line treatment of EGFR-mutant, PD-L1 positive NSCLC patients. Stage 2 enrollment is underway, aiming to confirm efficacy in a larger cohort. Overall survival data remain immature and will be presented in the future. The study supports dose escalation of third-generation EGFR TKIs as a promising approach for this difficult-to-treat patient subset.

Asset Subtitle

Hui Yu

Meta Tag

Speaker Hui Yu

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

FUTURE trial

firmonertinib

EGFR tyrosine kinase inhibitor

non-small cell lung cancer

EGFR exon 19 deletions

L858R mutations

PD-L1 expression

progression-free survival

overall response rate

treatment-related adverse events