sotorasib + tarloxotinib

Sotorasib + tarloxotinib is an investigational combination therapy for cancer, primarily being studied in non-small cell lung cancer (NSCLC) and other solid tumors with specific genetic alterations. Sotorasib is a first-in-class, orally available small molecule that selectively and irreversibly inhibits the KRAS G12C mutant protein by covalently binding to the cysteine residue unique to this mutation, thereby trapping KRAS G12C in its inactive GDP-bound state and blocking oncogenic signaling[1][5][6]. It is approved as monotherapy for advanced or metastatic NSCLC with KRAS G12C mutations after prior treatment[3][7]. Tarloxotinib is a hypoxia-activated prodrug of a pan-ErbB kinase inhibitor; under low oxygen conditions typical of tumor microenvironments, it releases an active inhibitor targeting multiple members of the ErbB family (including EGFR, HER2/ERBB2, HER4/ERBB4), showing activity against tumors harboring EGFR exon 20 insertions or HER2 activating mutations[4]. The combination aims to target both primary oncogenic drivers (KRAS G12C) and bypass resistance pathways mediated by ErbB family kinases. Both drugs are being developed for use in patients whose cancers have progressed on standard therapies.

Other names

sotorasibtarloxotinib