2022 World Conference on Lung Cancer (ePosters)-EP08.02-019. Phase 1/2 Study of BLU-701, a Highly Selective EGFR Inhibitor, in Patients With EGFR-Mutant Non-Small Cell Lung Cancer

EP08.02-019. Phase 1/2 Study of BLU-701, a Highly Selective EGFR Inhibitor, in Patients With EGFR-Mutant Non-Small Cell Lung Cancer

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The HARMONY trial is a global phase 1/2 study evaluating the safety, tolerability, pharmacokinetics, and antitumor activity of BLU-701 in patients with EGFR-mutant non-small cell lung cancer (NSCLC). EGFR mutations, specifically exon 19 deletions and L858R substitutions, are common driver mutations in NSCLC. Although third-generation tyrosine kinase inhibitors (TKIs) like osimertinib have improved outcomes, resistance eventually develops, including the emergence of the EGFR C797X mutation for which there are no approved TKIs. BLU-701 is an investigational, reversible, brain-penetrant oral TKI that selectively targets activating EGFR mutations and C797X resistance mutations, with high potency and selectivity for these mutants over wildtype EGFR. Preclinical studies have shown promising antitumor activity of BLU-701 in treatment-naïve and osimertinib-resistant tumor models. The HARMONY trial consists of a dose-escalation phase (Part 1) to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of BLU-701 as monotherapy or in combination with osimertinib or platinum-based chemotherapy. The primary endpoints of the trial include the MTD, RP2D, and safety in Part 1, and the overall response rate (ORR) in Part 2. The trial is ongoing and planned for approximately 30 centers worldwide. The study design includes a Bayesian optimal interval (BOIN) design in the dose-escalation phase to determine the MTD and RP2D based on dose-limiting toxicities, pharmacokinetics, pharmacodynamics, cumulative toxicity, and antitumor activity. The trial aims to investigate the safety and efficacy of BLU-701 in patients with EGFR-mutant NSCLC, either as monotherapy or in combination with osimertinib or platinum-based chemotherapy.

Asset Subtitle

Alexander Spira

Meta Tag

Speaker Alexander Spira

Topic Metastatic Non-small Cell Lung Cancer - Molecular Targeted Treatments

Keywords

Harmony trial

BLU-701

EGFR-mutant non-small cell lung cancer

EGFR mutations

exon 19 deletions

L858R substitutions

tyrosine kinase inhibitors

osimertinib

EGFR C797X mutation

reversible brain-penetrant oral TKI