Purpose: Selpercatinib, a first-in-class, highly selective, and potent CNS-active RET kinase inhibitor, is currently approved for the treatment of patients with fusion-positive non-small-cell lung cancer (NSCLC). We provide a registrational data set update in more than double (n = 316) of the original reported population (n = 144) and better characterization of long-term efficacy and safety.
Methods: Patients were enrolled to LIBRETTO-001, a phase I/II, single-arm, open-label study of selpercatinib in patients with -altered cancers.
Dysregulated MET signaling plays an important role in lung oncogenesis, tumor growth and invasiveness. It may occur through various mechanisms, such as MET overexpression or gene amplification or mutation, all of which can be detected by specific methods. The utility of MET overexpression as a biomarker remains unclear due to discrepancies in its occurrence and non-standardized cut-off thresholds.
View Article and Find Full Text PDFHepatocyte growth factor (HGF)/c-Met pathway dysregulation is a mechanism for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Ficlatuzumab (AV-299; SCH 900105), a humanized IgG κ HGF inhibitory monoclonal antibody, prevents HGF/c-Met pathway ligand-mediated activation. This phase 1b study assessed the safety/tolerability, pharmacokinetics/pharmacodynamics, and antitumor activity of ficlatuzumab plus gefitinib in Asian patients with previously treated advanced non-small cell lung cancer (NSCLC).
View Article and Find Full Text PDFThe critical role of lysine demethylase 4A (KDM4A), in regulating chromatin structure and consequently in driving cellular proliferation and oncogenesis has been the focus of recent studies. Non-small-cell lung cancer (NSCLC) patients with adenocarcinoma histology who were homozygous for KDM4A single nucleotide polymorphism (SNP)-A482 (rs586339) were recently shown to have significantly worse overall survival (OS) compared with patients with the wild-type or the heterozygous genotype at this locus (hazard ratio=1.68, P=0.
View Article and Find Full Text PDFIntroduction: Activating mutations in the EGFR gene have been shown to confer sensitivity to EGFR tyrosine kinase inhibitors in patients with advanced NSCLC. However, wide interpatient variability in treatment outcomes in response to EGFR tyrosine kinase inhibitors in these patients remains unaccounted for. This study aimed to evaluate the influence of EGFR mutation types and subtypes on survival outcomes in advanced Asian patients with NSCLC receiving first-line gefitinib therapy.
View Article and Find Full Text PDFPurpose: This study aimed to evaluate the safety, tolerability and pharmacokinetics of the combination of oral vinorelbine with erlotinib using the conventional (CSV) and metronomic (MSV) dosing schedules in patients with advanced non-small cell lung cancer (NSCLC).
Methods: This was an open-label, multiple dose-escalation phase I study. An alternating 3+3 phase I design was employed to allow each schedule to enroll three patients sequentially at each dose level.