News - MET Y1230C - LARVOL VERI

3ms

Landscape of MET activating alterations (METa) in advanced cancers (AC) using circulating tumor DNA (ctDNA) next-generation sequencing (NGS) in Asia and the Middle East (AME) (ESMO Asia 2024)

Co-fusions involved EML4-ALK (1.9%), STRN-ALK (1.2%), and CCDC6-RET (0.7%). Conclusions Comprehensive ctDNA NGS can identify METa and associated co-alterations that may inform therapeutic decisions for patients with AC in AME.

3 months ago

Next-generation sequencing • Circulating tumor DNA • Metastases

EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR3 (Fibroblast growth factor receptor 3) • EML4 (EMAP Like 4) • KIF5B (Kinesin Family Member 5B) • TACC3 (Transforming acidic coiled-coil containing protein 3) • CCDC6 (Coiled-Coil Domain Containing 6) • STRN (Striatin) • CDK6 (Cyclin-dependent kinase 6)

TP53 mutation • EGFR mutation • MET exon 14 mutation • ALK fusion • MET mutation • MET fusion • MET Y1230C • MET Y1230C

Guardant360® CDx

1year

Structural insight into the macrocyclic inhibitor TPX-0022 of c-Met and c-Src. (PubMed, Comput Struct Biotechnol J)

In addition, TPX-0022 exhibited potent activity against the resistance-relevant c-Met L1195F mutant and moderate activity against the c-Met G1163R, F1200I and Y1230H mutants but weak activity against the c-Met D1228N and Y1230C mutants. Overall, our study reveals the structural mechanism underlying the potency and selectivity of TPX-0022 and the ability to overcome acquire resistance mutations and provides insight into the development of selective c-Met macrocyclic inhibitors.

1 year ago

Journal

MET (MET proto-oncogene, receptor tyrosine kinase) • CSF1R (Colony stimulating factor 1 receptor)

MET mutation • MET D1228N • MET F1200I • MET Y1230C • MET Y1230C

elzovantinib (TPX-0022)

1year

Biophysical and structural characterization of the impacts of MET phosphorylation on tepotinib binding. (PubMed, J Biol Chem)

We corroborated these data with target engagement studies by fluorescence cross-correlation spectroscopy using KD constructs in cell lysates or full-length receptors from solubilized cellular membranes as wildtype or activated mutants (Y1235D and Y1234E/1235E). Collectively, our results provide further insight into the MET A-loop structural determinants that affect the binding of the selective inhibitor tepotinib.

1 year ago

Journal

HGF (Hepatocyte growth factor)

MET F1200I • MET Y1230C • MET Y1230C

Tepmetko (tepotinib)

over1year

Predictive Biomarkers of Response to REGN5093 to Guide Patient Selection in MET-Altered Advanced Non-small Cell Lung Cancer (IASLC-WCLC 2023)

We report biomarkers associated with clinical response and resistance to REGN5093 which may help with screening of aNSCLC pts in future combination studies of REGN5093 with other therapies.

over 1 year ago

Clinical • Metastases

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • JAK2 (Janus kinase 2)

EGFR mutation • BRAF mutation • MET amplification • KRAS G12D • PIK3CA H1047R • MET exon 14 mutation • MET overexpression • MET mutation • MET expression • KRAS G12 • JAK2 V617F • TP53 R248Q • EGFR mutation + MET-CEP7 fusion • MET Y1230C • MET D1228H • MET Y1230C

FoundationOne® CDx • TruSight Oncology 500 Assay

davutamig (REGN5093)