KRAS G12C inhibitor Pregnancy: There are no data from the use of sotorasib in pregnant women; animal studies have shown reproductive toxicity. Patients must be informed of the potential hazards to the foetus if it is used during pregnancy or if they become pregnant while taking it. It is unknown whether sotorasib or its metabolites are excreted in human milk — a decision must be made whether to discontinue breast-feeding or to discontinue/abstain from therapy.

Sotorasib (Specialist drug)

Brand names: Lumykras

Sotorasib is an oral targeted anticancer agent (a KRAS G12C inhibitor) used in adults with KRAS G12C-mutated advanced non-small-cell lung cancer after prior systemic therapy.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 960 mg (four 240 mg tablets)

Route: Oral — tablets normally swallowed whole, with or without food. Patients who have difficulty swallowing solids may disperse the tablets (without crushing) in 120 mL of non-carbonated room-temperature water, stir until dispersed into small pieces and drink immediately, then rinse the container with a further 120 mL of water and drink it; discard the dispersion if not drunk within 2 hours. The same dispersion process may be used for nasogastric or PEG tube administration with appropriate water flushes.

Frequency: Once daily at the same time each day; treatment is recommended until disease progression or unacceptable toxicity

Treatment must be initiated by a physician experienced in the use of anticancer medicinal products, and the presence of a KRAS G12C mutation must be confirmed using a validated test before starting. Missed doses: if less than 6 hours have passed since the scheduled dosing time, take the dose as normal; if more than 6 hours have passed, do not take it — continue as prescribed the next day. If vomiting occurs after a dose, do not take an additional dose that day. Dose reduction levels: starting dose 960 mg once daily; first reduction 480 mg (two 240 mg tablets) once daily; second reduction 240 mg (one 240 mg tablet) once daily. A maximum of two dose reductions is permitted, and treatment must be discontinued if the patient cannot tolerate the minimum dose of 240 mg once daily. Hepatotoxicity — AST or ALT >3x and up to 5x ULN (or >3x to 5x baseline if baseline abnormal) with symptoms, or AST or ALT >5x ULN (or >5x baseline) with or without symptoms: stop treatment until recovery to <=3x ULN or <=3x baseline, then resume at the next dose reduction level. AST or ALT >3x ULN with total bilirubin >2x ULN: permanently discontinue if no alternative cause is identified; if an alternative cause is identified, do not resume until AST/ALT/bilirubin return to baseline. ILD/pneumonitis (any grade): stop treatment if suspected and permanently discontinue if confirmed with no other cause identified. Grade >= 3 nausea, vomiting or diarrhoea despite appropriate supportive care, and other Grade >= 3 adverse reactions: stop treatment until recovery to <= Grade 1 or baseline, then resume at the next dose reduction level. Liver function tests (ALT, AST, alkaline phosphatase and total bilirubin) must be monitored before starting, every 3 weeks for the first 3 months, then monthly or as clinically indicated, with more frequent testing after recent immunotherapy and in serious hepatotoxicity. Hepatic impairment: no dose adjustment for mild (Child-Pugh A) or moderate (Child-Pugh B); dose adjustment should be considered in severe (Child-Pugh C), where there are no multiple-dose data and the medicine should be used with caution. Elderly: no dose adjustment. Contains lactose — patients with rare hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take it. Paediatric: safety and efficacy in children and adolescents aged less than 18 years have not been established; no data are available.

Dose adjustments

Renal

Based on population pharmacokinetic analysis, no dose adjustment is recommended for patients with mild renal impairment (creatinine clearance, CrCL, >= 60 mL/min). Sotorasib has not been studied in patients with moderate or severe renal impairment (CrCL < 60 mL/min).

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substance or to any of the excipients

Side effects

Diarrhoea (36.6%; Grade >= 3 in 6.9%)
Musculoskeletal pain (30.1%)
Nausea (24.7%) and vomiting (16.1%)
Fatigue (19.1%) and abdominal pain (18.2%)
Hepatotoxicity (18%), including increased ALT (Grade >= 3 in 5.9%) and increased AST (Grade >= 3 in 4.6%)
Also very common: cough (16.5%), anaemia, headache, dyspnoea, constipation, decreased appetite, peripheral oedema, pyrexia, hypokalaemia, hyponatraemia, hypocalcaemia. ILD/pneumonitis is common

Interactions

Acid-reducing agents — co-administration with a proton pump inhibitor (e.g. omeprazole) or an H2 receptor antagonist is addressed in §4.5, but the eMC §4.5 text was truncated at the source-fetch limit; the full interaction detail and any dosing separation advice were NOT retrieved — clinician to source

Clinical monograph

How it works

It binds irreversibly and selectively to the mutant KRAS G12C protein, locking it in an inactive state and blocking the downstream proliferative signalling driven by this oncogenic mutation.

Prescribing in practice

Hepatotoxicity is a key risk, so liver function must be checked before and during treatment and the drug interrupted or stopped for significant transaminase rises.
It can cause drug-induced interstitial lung disease/pneumonitis, which should prompt urgent assessment and withholding of therapy.
Acid-reducing agents and CYP3A4 inducers reduce sotorasib exposure, so co-prescribing should be reviewed against the SPC.

Monitoring

Monitor liver function tests regularly and watch for new or worsening respiratory symptoms suggestive of pneumonitis.

Counselling the patient

Report yellowing of the skin or eyes, dark urine, or new breathlessness and cough promptly.
Tell your team about all other medicines, including antacids and indigestion remedies, as they can reduce how well this drug works.
Take the tablets as directed and attend regular blood tests.

Evidence & guidelines

Efficacy in pretreated KRAS G12C-mutated non-small-cell lung cancer was demonstrated in dedicated registrational trials and is reflected in NICE guidance.

Reference: NICE TA781; SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways