Sotorasib (1 brand name, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- LUMAKRAS
Contraindications
None.
Adverse Reactions
The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Hepatotoxicity [see Warnings and Precautions (5.1)] Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.2)]
Mechanism of Action
Sotorasib is an inhibitor of KRAS G12C, a tumor-restricted, mutant-oncogenic form of the RAS GTPase, KRAS. Sotorasib forms an irreversible, covalent bond with the unique cysteine of KRAS G12C, locking the protein in an inactive state that prevents downstream signaling without affecting wild-type KRAS. Sotorasib blocked KRAS signaling, inhibited cell growth, and promoted apoptosis only in KRAS G12C tumor cell lines. Sotorasib inhibited KRAS G12C in vitro and in vivo with minimal detectable off-target activity. In mouse tumor xenograft models, sotorasib-treatment led to tumor regressions and prolonged survival, and was associated with anti-tumor immunity in KRAS G12C models. In the setting of KRAS G12C-mutant CRC, epidermal growth factor receptor (EGFR) activation has been identified as a mechanism of resistance to KRAS G12C inhibition. In a murine patient-derived colorectal tumor xenograft model, the combination of sotorasib and panitumumab, an EGFR antagonist, had increased antitumor activity compared to either sotorasib or panitumumab alone.