First-in-human study of AMG 193, an MTA-cooperative PRMT5 inhibitor, in patients with MTAP-deleted solid tumors: results from phase 1 dose exploration.

Date publication

septembre 2024

Journal

Annals of oncology : official journal of the European Society for Medical Oncology

Auteurs

Membres identifiés du Cancéropôle Est :
Pr GHIRINGHELLI François

Tous les auteurs :
Rodon J, Prenen H, Sacher A, Villalona-Calero M, Penel N, El Helali A, Rottey S, Yamamoto N, Ghiringhelli F, Goebeler ME, Doi T, Postel-Vinay S, Lin CC, Liu C, Chuang CH, Keyvanjah K, Eggert T, O'Neil BH

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/39293516

Résumé

Homozygous deletion of methylthioadenosine phosphorylase (MTAP) occurs in ∼10%-15% of solid tumors. AMG 193, a CNS-penetrant methylthioadenosine-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor, selectively induces synthetic lethality in MTAP-deleted tumors cells. Here, we report results of the completed monotherapy dose exploration evaluating AMG 193 in patients with MTAP-deleted solid tumors.

Mots clés

MTAP, PRMT5, methylthioadenosine phosphorylase, non-small cell lung cancer, pancreas cancer, protein arginine methyltransferase 5 synthetic lethality

Référence

Ann Oncol. 2024 09 2;: