WCLC 2025 - Posters & ePosters-P3.12.73 Phase I/II Study on WSD0922-FU in EGFR C797S+ NSCLC

Pdf Summary

This Phase I/II study evaluated WSD0922-FU, a novel oral, brain-penetrable, fourth-generation EGFR inhibitor targeting EGFR mutations including the resistant C797S mutation in non-small cell lung cancer (NSCLC) patients who progressed after first-line third-generation (3rd G) EGFR tyrosine kinase inhibitors (TKIs). The study enrolled 34 patients with confirmed EGFR C797S mutations, previously treated with 3rd G EGFR TKIs, and excluded those with EGFR T790M, MET mutations, or exon 20 insertions.<br /><br />Key efficacy findings at data cutoff (July 31, 2025) showed an overall objective response rate (ORR) of 58.9% and a disease control rate (DCR) of 97.1%. Among patients with brain metastases (n=7), the ORR was 57.1%, and DCR was 100%. The 120mg twice-daily dose cohort (n=19) demonstrated an ORR of 63.2% and DCR of 100%, with a 75% ORR in brain metastases. Responses were durable, with confirmed responses in 10 patients.<br /><br />Safety data revealed manageable adverse events without new safety signals compared to other EGFR TKIs. Common treatment-related adverse events (TRAEs) included rash, diarrhea, vomiting, and lymphocyte count decrease, with Grade 3 TRAEs occurring infrequently. There were no treatment discontinuations due to TRAEs or treatment-related deaths.<br /><br />The study supports WSD0922-FU’s potential as an effective and safe treatment for EGFR C797S-mutated NSCLC resistant to prior 3rd generation EGFR TKIs. Dose exploration from 80mg to 200mg has been adequate, with ongoing enrollment in expansion cohorts. Plans are underway for Phase IIb and Phase III studies to confirm efficacy and establish WSD0922-FU as a standard second- or third-line treatment in this patient population. This agent offers a promising new option for overcoming resistance mechanisms in EGFR-mutant NSCLC.

Asset Subtitle

Caicun Zhou

Meta Tag

Speaker Caicun Zhou

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

WSD0922-FU

EGFR C797S mutation

non-small cell lung cancer

third-generation EGFR TKIs resistance

brain-penetrable EGFR inhibitor

objective response rate

disease control rate

treatment-related adverse events

Phase I/II clinical trial

dose escalation study