WCLC 2025 - Posters & ePosters-P3.18.68 First-In-Human Trial of PFL-241/STX-241 in Patients With Locally Advanced or Metastatic NSCLC Resistant to EGFR Tyrosine Kinase Inhibitors

P3.18.68 First-In-Human Trial of PFL-241/STX-241 in Patients With Locally Advanced or Metastatic NSCLC Resistant to EGFR Tyrosine Kinase Inhibitors

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This document summarizes a Phase I/II open-label, first-in-human clinical trial (F60087CI101) evaluating the safety and efficacy of PFL-241/STX-241 in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) resistant to third-generation EGFR tyrosine kinase inhibitors (TKIs). EGFR mutations occur in 15-20% of NSCLC cases, with the C797X mutation commonly driving resistance to osimertinib, a third-generation TKI.<br /><br />PFL-241 is a novel, orally bioavailable, CNS-penetrant fourth-generation EGFR TKI designed to target major EGFR mutations (exon 19 deletion or L858R), including double mutants with C797X, but excluding T790M mutation carriers. Preclinical data show that PFL-241 has superior potency and selectivity compared to first-generation inhibitors (e.g., gefitinib) and maintains efficacy against EGFR C797X mutants resistant to osimertinib.<br /><br />The study includes two parts: Part 1 (dose escalation) aims to characterize safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity to identify the optimal biologically active dose (OBD) and maximum tolerated dose (MTD). Part 2 focuses on selecting the recommended Phase II dose (RP2D) and further characterizing safety and efficacy. Eligible patients must have confirmed advanced or metastatic EGFR-mutant NSCLC with disease progression after third-generation TKI therapy, measurable lesions, and good performance status. Key exclusions include patients with T790M mutation, symptomatic CNS metastases, or rapid progressive disease needing chemotherapy.<br /><br />The global trial involves 16 sites across Europe, the US, and Asia, with an expected primary completion in the second half of 2027. Sponsored by Pierre Fabre Medicament, the study aims to address a significant unmet need for effective treatment options against EGFR TKI-resistant mutant NSCLC, particularly those harboring C797X mutations refractory to current therapies. Initial in vivo models demonstrate promising anti-tumor effects, supporting ongoing clinical evaluation.

Asset Subtitle

Gerrina Ruiter

Meta Tag

Speaker Gerrina Ruiter

Topic Clinical Trials in Progress

Keywords

Phase I/II clinical trial

PFL-241

STX-241

non-small cell lung cancer

NSCLC

EGFR mutations

third-generation TKIs resistance

C797X mutation

fourth-generation EGFR TKI

osimertinib resistance