LUMYKRAS (Sotorasib)
Targeted Therapy for KRAS G12C-Mutated Non-Small Cell Lung Cancer
Quick Facts About LUMYKRAS
Key Takeaways About LUMYKRAS
- First-in-class targeted therapy: LUMYKRAS is the first approved drug to directly target and inhibit the KRAS G12C mutation, which was previously considered undruggable for over 40 years
- Requires genetic testing: A validated molecular test must confirm the KRAS G12C mutation in your tumour before treatment can begin – only about 13% of NSCLC patients carry this mutation
- Monitor liver function: Elevated liver enzymes (AST/ALT) are very common; your doctor will perform regular blood tests and may adjust the dose or stop treatment if liver problems occur
- Watch for lung inflammation: Interstitial lung disease (ILD) or pneumonitis can occur – report any new or worsening breathing problems, cough, or fever immediately
- Multiple drug interactions: Acid-reducing medications, certain anti-epileptics, and many other drugs can reduce or alter the effectiveness of LUMYKRAS – always inform your doctor of all medications you take
What Is LUMYKRAS and What Is It Used For?
LUMYKRAS (sotorasib) is a targeted anticancer medicine that treats adults with a specific type of lung cancer called non-small cell lung cancer (NSCLC). It is prescribed when the cancer has spread (metastatic) and carries a genetic mutation known as KRAS G12C, and when previous treatments have not stopped the cancer from growing.
LUMYKRAS contains the active substance sotorasib and belongs to a group of medicines known as antineoplastic agents (cancer medicines). It represents a groundbreaking advance in precision oncology, as it is the first approved medicine designed to specifically target and inhibit the KRAS G12C protein – a mutation that scientists had considered “undruggable” for over four decades since its discovery.
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for approximately 80–85% of all lung cancer cases worldwide. Among patients with NSCLC, approximately 13% harbour the KRAS G12C mutation. This genetic alteration causes the KRAS protein to become permanently stuck in its “on” position, sending continuous signals for cancer cells to grow and divide uncontrollably. The KRAS G12C mutation is particularly prevalent in patients with a history of smoking, though it can occur in non-smokers as well.
LUMYKRAS is indicated for adults whose advanced or metastatic NSCLC has progressed despite prior systemic therapy, which typically includes platinum-based chemotherapy and/or immune checkpoint inhibitors (immunotherapy). Your oncologist will verify the presence of the KRAS G12C mutation through a validated companion diagnostic test before initiating treatment. This test can be performed on a tumour tissue biopsy sample or, in some cases, through a blood sample (liquid biopsy) that detects circulating tumour DNA.
How Does LUMYKRAS Work?
The abnormal KRAS G12C protein is a critical driver of tumour cell growth. In its mutated form, it remains locked in an active state, continuously activating the RAS/MAPK signalling pathway – a key cascade that regulates cell proliferation, differentiation, and survival. Sotorasib works by forming an irreversible (covalent) bond with the mutant cysteine residue at position 12 of the KRAS protein. This locks the KRAS G12C protein in its inactive, GDP-bound state and prevents it from switching back to the active form.
By shutting down this aberrant signalling, sotorasib effectively disrupts the molecular machinery that drives tumour growth, leading to inhibition of cancer cell proliferation and, in many cases, shrinkage of the tumour. Clinical studies have demonstrated that sotorasib can achieve meaningful tumour responses in previously treated NSCLC patients who carry the KRAS G12C mutation, with an overall response rate of approximately 28–37% and disease control rates of around 80% in the pivotal CodeBreaK 100 trial.
LUMYKRAS received conditional marketing authorisation from the European Medicines Agency (EMA) in January 2022 and accelerated approval from the United States Food and Drug Administration (FDA) in May 2021. The conditional approval means that the manufacturer is required to provide further data from ongoing clinical trials. LUMYKRAS was developed by Amgen and represents a new class of targeted therapies that directly block mutant KRAS proteins.
What Should You Know Before Taking LUMYKRAS?
Before starting LUMYKRAS, inform your oncologist about all your medical conditions, especially any history of liver disease or lung problems. Your doctor will perform blood tests to assess your liver function before treatment and will monitor it regularly throughout therapy. LUMYKRAS should not be used in patients who are allergic to sotorasib or any of its excipients.
Contraindications
You should not take LUMYKRAS if:
- You are allergic to sotorasib or any of the other ingredients in the tablet (listed in the contents section below). Signs of an allergic reaction may include skin rash, itching, swelling, or difficulty breathing.
There are no other absolute contraindications listed for LUMYKRAS. However, the decision to start treatment must be made by a specialist oncologist after careful evaluation of your overall health, tumour characteristics, and previous treatment history.
Warnings and Precautions
Talk to your oncologist, pharmacist, or nurse before taking LUMYKRAS if any of the following apply to you:
Liver problems (hepatotoxicity): LUMYKRAS can cause serious liver damage. Your doctor will take blood tests before starting treatment and regularly during treatment to check your liver function. If your liver enzyme levels become elevated, your doctor may decide to reduce the dose of LUMYKRAS, temporarily interrupt treatment, or stop it permanently. Tell your doctor immediately if you develop signs of liver problems, such as yellowing of the skin or whites of the eyes (jaundice), dark urine, unusual tiredness, nausea, vomiting, loss of appetite, or pain in the upper right area of the abdomen.
Lung problems (interstitial lung disease/pneumonitis): Some lung problems may worsen during treatment with LUMYKRAS, as the medicine can cause inflammation of the lungs. Symptoms may resemble those of lung cancer itself. Tell your doctor immediately if you develop new or worsening symptoms such as difficulty breathing, shortness of breath, cough (with or without mucus), or fever. Your doctor may need to interrupt or permanently discontinue treatment if interstitial lung disease is confirmed.
Kidney problems: Uncommonly, LUMYKRAS may cause kidney problems, including kidney failure. Your doctor may monitor your kidney function during treatment.
Use in Children and Adolescents
LUMYKRAS has not been studied in children or adolescents. Treatment with LUMYKRAS is not recommended for patients under 18 years of age. The safety and efficacy of sotorasib in the paediatric population have not been established, and KRAS G12C-mutated NSCLC is extremely rare in young patients.
Pregnancy and Breastfeeding
Pregnancy: If you are pregnant, think you might be pregnant, or are planning to become pregnant, consult your oncologist before taking LUMYKRAS. You should not become pregnant while taking this medicine, as the effects of sotorasib on the developing baby are not known and potential harm cannot be ruled out. If you are of childbearing potential, you must use a highly effective method of contraception during treatment and for at least 7 days after the last dose. Hormonal contraceptives taken by mouth may be less effective when used with LUMYKRAS – you should also use a barrier method (such as condoms) to prevent pregnancy. Discuss suitable contraceptive options with your doctor.
Breastfeeding: You should not breastfeed during treatment with LUMYKRAS and for 7 days after the last dose. It is not known whether sotorasib or its metabolites pass into breast milk, and a risk to the nursing infant cannot be excluded.
Driving and Operating Machinery
LUMYKRAS has no known significant effect on the ability to drive or use machines. However, some patients may experience fatigue or dizziness as side effects. If you are affected, do not drive or operate machinery until these symptoms resolve.
Important Information About Ingredients
Lactose: LUMYKRAS tablets contain lactose monohydrate. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
Sodium: This medicine contains less than 1 mmol (23 mg) sodium per tablet, which means it is essentially sodium-free.
How Does LUMYKRAS Interact with Other Drugs?
LUMYKRAS has clinically significant interactions with numerous medications, including acid-reducing drugs, certain anti-epileptics, HIV medications, immunosuppressants, anticoagulants, and many others. Always tell your oncologist about all medications, vitamins, and herbal supplements you are taking or plan to take.
Sotorasib is primarily metabolised by the liver enzyme CYP3A4 and is also a substrate of the P-glycoprotein (P-gp) transporter. Importantly, sotorasib acts as an inducer of CYP3A4, meaning it can reduce the blood levels and effectiveness of many other drugs metabolised through this pathway. It also inhibits certain drug transporters (BCRP, MATE1, MATE2-K, OATP1B1, OATP1B3), which can increase the levels of substrate drugs. These complex pharmacokinetic interactions make careful medication review essential before and during treatment.
Drugs That Reduce the Effectiveness of LUMYKRAS
| Drug / Class | Examples | Mechanism | Recommendation |
|---|---|---|---|
| Proton Pump Inhibitors (PPIs) | Omeprazole, lansoprazole, esomeprazole, pantoprazole, rabeprazole | Reduced gastric acidity decreases sotorasib absorption | Take LUMYKRAS with an acidic drink (e.g. cola) if a PPI is needed |
| H2 Receptor Antagonists | Famotidine, ranitidine, cimetidine | Reduced gastric acidity decreases sotorasib absorption | Take LUMYKRAS with an acidic drink (e.g. cola) if an H2 blocker is needed |
| Local Antacids | Magnesium hydroxide, calcium carbonate, aluminium hydroxide | Reduced gastric acidity decreases sotorasib absorption | Take LUMYKRAS 4 hours before or 10 hours after the antacid |
| Strong CYP3A4 Inducers | Rifampicin, phenytoin, carbamazepine, phenobarbital, enzalutamide | Increased metabolism of sotorasib reduces its blood levels | Avoid concomitant use; discuss alternatives with your doctor |
| Herbal Products | St. John’s Wort (Hypericum perforatum) | CYP3A4 inducer that reduces sotorasib effectiveness | Avoid use during LUMYKRAS treatment |
Drugs Whose Effectiveness May Be Reduced by LUMYKRAS
| Drug / Class | Examples | Mechanism | Clinical Impact |
|---|---|---|---|
| Opioid Analgesics | Alfentanil, fentanyl | CYP3A4 induction by sotorasib | Reduced pain relief; dose adjustment may be needed |
| Immunosuppressants | Cyclosporine, sirolimus, everolimus, tacrolimus | CYP3A4 induction by sotorasib | Risk of organ rejection; monitor levels closely |
| Calcium Channel Blockers | Amlodipine, manidipine | CYP3A4 induction by sotorasib | Reduced blood pressure control |
| Statins | Simvastatin, atorvastatin, lovastatin | CYP3A4 induction by sotorasib | Reduced cholesterol-lowering effect |
| Benzodiazepines | Midazolam | CYP3A4 induction by sotorasib | Reduced sedation/anxiolytic effect |
| Antiarrhythmics | Dronedarone, amiodarone | CYP3A4 induction by sotorasib | Reduced efficacy in controlling heart rhythm |
| Anticoagulants | Rivaroxaban, apixaban | CYP3A4 induction by sotorasib | Reduced anticoagulation; increased clot risk |
| Oral Contraceptives | Combined hormonal contraceptives | CYP3A4 induction by sotorasib | May become ineffective; use barrier method additionally |
Drugs Whose Levels May Be Increased by LUMYKRAS
| Drug / Class | Examples | Mechanism | Clinical Impact |
|---|---|---|---|
| Antimetabolites / Chemotherapy | Methotrexate, mitoxantrone, topotecan, lapatinib | Inhibition of BCRP and/or OATP transporters | Increased risk of side effects; monitor closely |
| Cardiac Glycosides | Digoxin | Inhibition of P-gp transporter | Risk of digoxin toxicity; monitor serum digoxin levels |
| Statins | Rosuvastatin | Inhibition of BCRP transporter | Increased risk of statin-related muscle problems |
Given the extensive interaction profile of LUMYKRAS, it is essential that your oncologist conducts a comprehensive review of all your current medications, including over-the-counter drugs, vitamins, and herbal supplements, before starting treatment and at each follow-up visit. Dose adjustments or alternative medications may be necessary to ensure both the effectiveness and safety of your treatment regimen.
What Is the Correct Dosage of LUMYKRAS?
The recommended dose is 960 mg (eight 120 mg tablets) taken once daily by mouth, at the same time each day, with or without food. Do not change your dose or stop taking LUMYKRAS unless your oncologist tells you to.
Always take LUMYKRAS exactly as your oncologist or pharmacist has instructed. Do not change your dose or stop treatment without your doctor’s guidance. Your oncologist may reduce the dose, temporarily interrupt treatment, or discontinue LUMYKRAS permanently depending on how well you tolerate the medicine and whether you develop certain side effects, particularly liver problems or lung inflammation.
Adults
Standard Dosing
Recommended dose: 960 mg once daily (eight 120 mg tablets or four 240 mg tablets)
Administration: Take your daily dose by mouth once per day at the same time each day
With or without food: LUMYKRAS can be taken with or without food
Swallow tablets whole: The tablets may be dispersed in water but must not be chewed, crushed, or split
If You Cannot Swallow Tablets Whole
Place your daily dose of LUMYKRAS tablets in half a glass (at least 120 ml) of room temperature, plain drinking water – do not crush the tablets. Stir gently until the tablets break into small pieces (they will not dissolve completely). The mixture may appear light yellow to clear yellow. Drink the mixture immediately. Rinse the glass with another half glass of water and drink it to ensure you receive the full dose. If you do not drink the entire mixture immediately, stir again before drinking. Consume the complete mixture within two hours of preparation. If medically necessary, LUMYKRAS may also be administered through a feeding tube (nasogastric tube) as directed by your healthcare team.
Taking LUMYKRAS with Acid-Reducing Medications
If you need to take a proton pump inhibitor (PPI) or an H2 receptor antagonist, take LUMYKRAS with an acidic drink (e.g. cola) to maintain adequate absorption. Alternatively, if you are using a local antacid (such as magnesium hydroxide or calcium carbonate), take LUMYKRAS either 4 hours before or 10 hours after the antacid.
Children and Adolescents
LUMYKRAS is not recommended for use in patients under 18 years of age. No data are available on the use of sotorasib in the paediatric population.
Elderly Patients
No dose adjustment is required for elderly patients. In clinical trials, approximately 44% of participants were aged 65 years or older. There were no clinically meaningful differences in the safety or efficacy of sotorasib between older and younger adults. Standard dosing of 960 mg once daily applies regardless of age.
Dose Modifications for Side Effects
Your oncologist may reduce your dose or temporarily interrupt treatment depending on the severity of side effects. Typical dose reduction steps are:
- First dose reduction: 480 mg once daily (four 120 mg tablets)
- Second dose reduction: 240 mg once daily (two 120 mg tablets)
If you cannot tolerate the lowest dose of 240 mg daily, your doctor will permanently discontinue LUMYKRAS and discuss alternative treatment options.
Missed Dose
If you forget to take LUMYKRAS at your usual time and less than 6 hours have passed, take the dose as normal. If more than 6 hours have passed since your scheduled dose, skip the missed dose entirely. Take your next dose at the usual time the following day. Do not take a double dose to make up for a missed one.
Vomiting After Taking LUMYKRAS
If you vomit after taking a dose of LUMYKRAS, do not take an additional dose. Simply take your next dose at the normally scheduled time.
Overdose
If you take more LUMYKRAS tablets than recommended, contact your oncologist, pharmacist, or nurse immediately. Taking an excessive dose may increase the risk and severity of side effects, particularly liver damage and gastrointestinal symptoms. Seek medical attention promptly and bring your medicine packaging with you so the healthcare team can identify what you have taken.
What Are the Side Effects of LUMYKRAS?
The most common side effects of LUMYKRAS include diarrhoea, nausea, fatigue, liver enzyme elevation, vomiting, constipation, abdominal pain, joint pain, back pain, shortness of breath, cough, decreased appetite, and anaemia. Serious side effects include hepatotoxicity (liver damage) and interstitial lung disease (ILD).
Like all medicines, LUMYKRAS can cause side effects, although not everybody gets them. Some side effects can be serious and may require your oncologist to adjust your treatment. Regular blood tests and clinical assessments are an essential part of monitoring during LUMYKRAS therapy.
- Yellowing of the skin or whites of the eyes, dark urine, severe nausea, or pain in the upper right abdomen (possible liver damage)
- New or worsening shortness of breath, cough with or without mucus, or fever (possible interstitial lung disease/pneumonitis)
- Significantly reduced urine output, swelling, or unexplained fatigue (possible kidney problems)
Very Common
May affect more than 1 in 10 people
- Diarrhoea
- Nausea
- Fatigue (feeling tired or weak)
- Vomiting
- Constipation
- Abdominal (stomach) pain
- Joint pain (arthralgia)
- Back pain
- Shortness of breath (dyspnoea)
- Cough
- Anaemia (low red blood cell count, causing tiredness)
- Decreased appetite
- Elevated liver enzymes (AST/ALT) – detected by blood tests
Common
May affect up to 1 in 10 people
- Headache
- Fever (pyrexia)
- Elevated alkaline phosphatase (blood test finding)
- Elevated bilirubin (blood test finding)
- Elevated gamma-glutamyltransferase (GGT) (blood test finding)
- Liver damage (hepatotoxicity)
- Interstitial lung disease (ILD) / pneumonitis (lung inflammation)
- Low potassium levels in the blood (hypokalaemia)
Uncommon
May affect up to 1 in 100 people
- Kidney problems, including kidney failure (renal impairment)
- Hepatitis (inflammation of the liver)
The liver enzyme elevations (AST/ALT) are among the most important side effects to monitor, as they can indicate potentially serious liver damage. Your oncologist will perform regular blood tests (typically before starting treatment, every 3 weeks for the first 3 months, and then monthly or as clinically indicated) to monitor your liver function. Based on the severity of any elevation, your doctor may choose to continue treatment at the same dose, reduce the dose, temporarily interrupt treatment, or permanently discontinue LUMYKRAS.
Interstitial lung disease (ILD) or pneumonitis, although less common, is a potentially life-threatening side effect. If confirmed, your doctor will permanently discontinue LUMYKRAS. It is crucial to report any new respiratory symptoms promptly, as early detection and management are essential for a better outcome.
If you experience any side effects not listed here, or if any side effect becomes severe, contact your oncologist or pharmacist. Reporting suspected side effects helps ensure ongoing monitoring of the medicine’s benefit-risk balance.
How Should You Store LUMYKRAS?
Store LUMYKRAS at room temperature in its original packaging, out of the reach and sight of children. No special storage conditions are required. Do not use after the expiry date printed on the carton and blister.
Keep LUMYKRAS tablets in their original packaging to protect them from moisture and light. No special temperature-controlled storage is necessary. Always check the expiry date (marked “EXP” on the carton and blister pack) before taking any tablets. The expiry date refers to the last day of the stated month.
Do not dispose of LUMYKRAS through household waste or down the drain. Cancer medicines require special handling for disposal. Ask your pharmacist about local programmes for the safe return of unused or expired medications. These measures help protect the environment and prevent accidental exposure.
What Does LUMYKRAS Contain?
Each LUMYKRAS 120 mg film-coated tablet contains 120 mg of the active substance sotorasib, along with inactive ingredients including microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, and magnesium stearate.
Active Substance
Each film-coated tablet contains 120 mg sotorasib.
Inactive Ingredients (Excipients)
The tablet core contains:
- Microcrystalline cellulose (E460(i))
- Lactose monohydrate
- Croscarmellose sodium (E468)
- Magnesium stearate (E470b)
The film coating contains:
- Poly(vinyl alcohol) (E1203)
- Titanium dioxide (E171)
- Macrogol 4000 (E1521)
- Talc (E553b)
- Yellow iron oxide (E172)
Appearance and Packaging
LUMYKRAS 120 mg film-coated tablets are yellow, oblong tablets, embossed with “AMG” on one side and “120” on the other. They are supplied in blister packs of 8 tablets per blister, in cartons of 240 tablets (30 blisters), as well as in multi-packs of 720 tablets (3 × 240). LUMYKRAS is also available in bottles of 120 tablets, supplied as 240 tablets (1 carton with 2 bottles). A 240 mg film-coated tablet is also available. Not all pack sizes may be marketed in all countries.
Frequently Asked Questions About LUMYKRAS
LUMYKRAS (sotorasib) is a targeted cancer therapy used to treat adults with advanced or metastatic non-small cell lung cancer (NSCLC) that carries a specific genetic mutation called KRAS G12C. It is prescribed when previous treatments, such as chemotherapy or immunotherapy, have not stopped the cancer from growing. A validated molecular test must confirm the KRAS G12C mutation in your tumour before treatment can begin.
Before starting LUMYKRAS, your tumour must be tested and confirmed to have the KRAS G12C mutation. This can be done using a validated molecular test on a tumour tissue biopsy or through a liquid biopsy (blood test) that detects circulating tumour DNA. Only approximately 13% of NSCLC patients carry this specific mutation. Without a confirmed KRAS G12C mutation, LUMYKRAS will not be effective and should not be prescribed.
Acid-reducing medications such as proton pump inhibitors (omeprazole, lansoprazole) and H2 receptor antagonists (famotidine, cimetidine) can reduce the absorption and effectiveness of LUMYKRAS. If you must take a PPI or H2 blocker, take LUMYKRAS with an acidic drink such as cola. If using a local antacid (e.g. magnesium hydroxide or calcium carbonate), take LUMYKRAS 4 hours before or 10 hours after the antacid to avoid this interaction.
If you miss a dose and it has been less than 6 hours since your scheduled time, take the dose as usual. If more than 6 hours have passed, skip the missed dose entirely and take your next dose at the normal scheduled time the following day. Do not take a double dose to compensate. If you vomit after taking LUMYKRAS, do not take an additional dose – simply take the next dose at the scheduled time.
In the pivotal CodeBreaK 100 clinical trial, LUMYKRAS achieved an overall response rate of approximately 28–37% in patients with previously treated KRAS G12C-mutated NSCLC, with a disease control rate of around 80%. This means that the tumour shrank significantly in about one-third of patients, and the disease was stabilised in the majority. The median duration of response was approximately 10 months. While LUMYKRAS does not cure cancer, it can provide meaningful disease control and symptom improvement for patients who have limited treatment options.
No. LUMYKRAS has not been studied in children or adolescents under 18 years of age and is not approved for paediatric use. The KRAS G12C mutation in NSCLC is primarily an adult condition, and there are no safety or efficacy data for sotorasib in the paediatric population.
References and Medical Sources
- European Medicines Agency (EMA). LUMYKRAS (sotorasib) – Summary of Product Characteristics. Last updated October 2024. Available at: ema.europa.eu/LUMYKRAS
- Skoulidis F, Li BT, Dy GK, et al. Sotorasib for Lung Cancers with KRAS p.G12C Mutation. New England Journal of Medicine. 2021;384(25):2371–2381. doi:10.1056/NEJMoa2103695
- U.S. Food and Drug Administration (FDA). FDA grants accelerated approval to sotorasib for KRAS G12C mutated NSCLC. May 2021. Available at: fda.gov
- de Langen AJ, Johnson ML, Mazieres J, et al. Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRAS G12C mutation: a randomised, open-label, phase 3 trial (CodeBreaK 200). The Lancet. 2023;401(10378):733–746. doi:10.1016/S0140-6736(23)00221-0
- ESMO Clinical Practice Guidelines. Metastatic Non-Small Cell Lung Cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Annals of Oncology. 2023.
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 3.2025.
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List (2023). Geneva: WHO; 2023.
- Hong DS, Fakih MG, Strickler JH, et al. KRAS G12C Inhibition with Sotorasib in Advanced Solid Tumors. New England Journal of Medicine. 2020;383(13):1207–1217. doi:10.1056/NEJMoa1917239
Editorial Team and Medical Review
Medical Content
iMedic Medical Editorial Team
Specialist physicians in oncology, clinical pharmacology, and internal medicine
Medical Review
iMedic Medical Review Board
Independent panel reviewing content per EMA, FDA, ESMO, and NCCN guidelines
Evidence Level: 1A – Based on systematic reviews, randomised controlled trials (CodeBreaK 100, CodeBreaK 200), and international clinical practice guidelines (ESMO, NCCN).
Funding: No commercial funding. Independent medical editorial content. No pharmaceutical company sponsorship.