Pierre Fabre Laboratories and Scorpion Therapeutics have announced the dosing of the first patient in a Phase I/II clinical trial evaluating PFL-241/STX-241 for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR Exon 19 or 21 mutations with the co-occurring C797S mutation. This mutation is a known resistance mechanism to third-generation EGFR inhibitors. PFL-241/STX-241 is a highly selective, orally bioavailable tyrosine kinase inhibitor (TKI) targeting the epidermal growth factor receptor (EGFR).
The Phase I/II trial is an open-label, multi-center study designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical efficacy of PFL-241/STX-241 as a monotherapy. The trial includes dose-escalation, dose-optimization, and dose-expansion phases.
Significance of EGFR Mutations in NSCLC
NSCLC is the most prevalent type of lung cancer, and EGFR mutations are significant drivers of the disease, occurring in up to 38% of tumors, depending on geographical location. The development of resistance to existing EGFR inhibitors, particularly through the C797S mutation, represents a critical unmet need in this patient population.
Expert Commentary
"We are eager to begin the clinical evaluation of PFL-241/STX-241, our mutant-selective 4th generation EGFR inhibitor, a molecule with differentiated properties that we believe has the potential to become a best-in-class therapeutic option for patients developing resistance to current targeted therapy," said Francesco Hofmann, Head of Research and Development for Medical Care at Pierre Fabre Laboratories. "The initiation of this clinical trial highlights our team's engagement and execution in strong partnership with Scorpion Therapeutics, and we look forward to demonstrating how patients could potentially benefit from this targeted therapy."
Trial Design and Objectives
The primary objectives of the Phase I/II trial are to determine the recommended Phase 2 dose (RP2D) and to assess the safety and tolerability of PFL-241/STX-241. Secondary objectives include evaluating the PK and PD of the drug, as well as assessing preliminary clinical efficacy, including objective response rate (ORR), duration of response (DoR), and progression-free survival (PFS).
