Combined SHP2 and KRAS G12C inhibitor therapy in patients with non-small-cell lung cancer
Mené en Chine sur 194 patients atteints d'une tumeur de stade localement avancé ou métastatique avec mutation G12C au niveau du gène KRAS (dont 171 patients atteints d'un cancer du poumon non à petites cellules), cet essai multicentrique de phase I/IIA détermine la dose maximale tolérée du glécirasib (un inhibiteur de KRAS G12C) en combinaison avec le sitnéprotafib (un inhibiteur de SHP2), puis évalue l'efficacité, du point de vue du taux de réponse globale, de cette combinaison
Decades of research on the first oncogene, rat sarcoma virus (RAS), have yielded breakthroughs in treating cancers driven by KRASG12C (ie, KRAS Gly12Cys).1 Multiple KRASG12C inhibitors have been approved for several indications, including as monotherapy in patients with previously treated KRASG12C-mutated non-small-cell lung cancer (NSCLC) and in combination with anti-EGFR monoclonal antibodies in patients with colorectal cancer. Although the approval of KRASG12C inhibitors represents the first targeted therapeutic approach for KRASG12C-mutated cancers, the efficacy of such inhibitors in monotherapy is limited to objective response rates (ORRs) of 10−43% and a median progression-free survival of 4·0−6·9 months.
The Lancet Respiratory Medicine , commentaire, 2025