2024 World Conference on Lung Cancer (WCLC) - Posters-P3.12D.03 A Study to Investigate Safety, PK, And Anti-Tumor Activity of TRX-221 In EGFR Mutant NSCLC: TRX-221-001 In Progress

P3.12D.03 A Study to Investigate Safety, PK, And Anti-Tumor Activity of TRX-221 In EGFR Mutant NSCLC: TRX-221-001 In Progress

Back to course

Pdf Summary

The ongoing TRX-221-001 study investigates the safety, pharmacokinetics (PK), and anti-tumor efficacy of TRX-221, a 4th-generation EGFR tyrosine kinase inhibitor (TKI), in patients with EGFR-mutant non-small cell lung cancer (NSCLC). Patients with NSCLC, particularly those exhibiting resistance to existing 3rd-generation EGFR-TKIs like osimertinib due to the EGFR C797S mutation, may benefit from this new treatment which has shown promise in preclinical models resistant to osimertinib.<br /><br />The study comprises three parts: Phase 1 Part A (dose escalation), Phase 1 Part B (dose exploration), and Phase 2 (dose expansion). Phase 1 Part A aims to determine the maximum tolerated dose (MTD) of TRX-221 through a Bayesian Optimal Interval (BOIN) design. Initial indications are positive, as no dose-limiting toxicities (DLT) or treatment-emergent adverse events (TEAE) have been reported in the first cohort at a dosage of 25 mg once daily. Phase 1 Part B will involve approximately 40 patients to further explore dose, while Phase 2 will expand to additional patients to confirm the recommended phase 2 dose (RP2D), particularly in those with difficult-to-treat mutations like C797X and T790M.<br /><br />The study is conducted in multiple centers in South Korea, with institutions such as Yonsei Cancer Center and Samsung Medical Center involved. TRX-221 demonstrates potent inhibition across various EGFR mutations, showing significant tumor regression in resistant xenograft models in preclinical trials. Enrolled patients will receive TRX-221 daily for a 21-day cycle, continuing treatment based on efficacy and safety assessments.<br /><br />The initial results are promising, indicating that TRX-221 could overcome resistance mechanisms in NSCLC and offer an effective treatment option for patients who have progressed after other therapies. Further data from ongoing dose escalation will help define the optimal dosing for subsequent trial phases.

Asset Subtitle

Sun Min Lim

Meta Tag

Speaker Sun Min Lim

Topic Metastatic NSCLC – Targeted Therapy

Keywords

TRX-221

EGFR

non-small cell lung cancer

tyrosine kinase inhibitor

C797S mutation

dose escalation

maximum tolerated dose

Bayesian Optimal Interval

tumor regression

South Korea