Sotorasib (unofficial Chinese translation: sotolacib/sotoracib), sold under the brand names Lumakras and Lumykras, is an anti-cancer drug used to treat non-small cell lung cancer (NSCLC). It targets a specific mutation in the protein KRAS, G12C, which is the cause of various forms of cancer.
The most common side effects include diarrhea, musculoskeletal pain, nausea, fatigue, liver damage, and cough.
Sotorasib is an inhibitor of the RAS GTPase family.
Sotorasib is the first targeted therapy approved for the treatment of tumors with any KRAS mutation, which accounts for approximately 25% of mutations in non-small cell lung cancer. KRAS G12C mutations account for approximately 13% of mutations in non-small cell lung cancer. sotorasib is approved for medical use in the United States in May 2021.
Sotorasib is being developed by AMGen, an Amgen company. phase I clinical trials are due to be completed in 2020. phase II clinical trials are approved to begin in December 2019.
Since G12C KRAS mutations are more common in some cancer types, 14% of patients with non-small cell lung cancer adenocarcinoma and 5% of colorectal cancer patients, and sotorasib is the first drug candidate to target this mutation, expectations have been high. The FDA has granted fast track designation to sotorasib for the treatment of metastatic non-small cell lung cancer with the G12C KRAS mutation.
Sotorasib can exist in two atropisomeric forms, one of which is more active than the other. It selectively forms irreversible covalent bonds with the sulfur atom in the cysteine residue that is present in the mutant form of KRAS but not in the normal form.
In November 2021, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a conditional marketing authorisation for the drug Lumykras for the treatment of patients with KRAS G12C mutations in non-small cell lung cancer (NSCLC).