Indications
Sotorasib is used to treat adults whose non-small cell lung cancer (NSCLC) has a KRAS G12C mutation and is either locally advanced or has spread (metastatic). The mutation must be confirmed by an FDA-approved test, and the person must already have had at least one earlier systemic therapy.
⚠️ Always consult a registered physician before taking any medicine.
Pharmacology
Sotorasib is a potent and highly selective inhibitor of KRASG12C (Kirsten rat sarcoma viral oncogene homolog). It binds covalently and irreversibly to the unique cysteine of KRASG12C. Once KRASG12C is inactivated, tumour cell signalling and survival are blocked, cell growth is inhibited, and apoptosis is promoted, but only in tumours that carry KRASG12C. This mutation is an oncogenic driver of tumourigenesis across multiple cancer types. The binding is unique because it involves both the P2 pocket and the His95 surface groove, and this strengthens the potency and selectivity. It locks the protein in an inactive state, which prevents downstream signalling, and wild-type KRAS is not affected. In vitro and in vivo studies showed inhibition of KRASG12C with minimal detectable off-target activity against other cellular proteins and processes. In numerous pre-clinical models expressing KRASG12C, the medicine impaired oncogenic signalling and tumour cell survival at clinically relevant exposures. Sotorasib also increased antigen presentation and inflammatory cytokine production, and only in tumour cells with KRASG12C. It induced anti-tumour inflammatory responses and immunity, and this drove permanent and complete tumour regressions in immunocompetent mice implanted with tumours expressing KRASG12C.
Pregnancy & Breastfeeding
Pregnancy: There are no data on the use of Sotorasib in pregnant women. Studies in animals have shown reproductive toxicity. Patients must be told about the possible hazards to the foetus if Sotorasib is used during pregnancy, or if the patient becomes pregnant while she is taking it.
Breast-feeding: We don't know if Sotorasib or its metabolites pass into human milk, so a risk to newborns and infants can't be excluded. A decision must be made either to stop breast-feeding or to stop or abstain from Sotorasib therapy. This decision should take into account the benefit of breast-feeding for the child and the benefit of the therapy for the woman.
⚠️ Talk to your doctor before taking any medicine during pregnancy or while breastfeeding.
Dosage Reference
⚠️ Reference ranges from official sources only. Consult your doctor for personalized dosing.