sotorasib
Lumakras (sotorasib) is a first-in-class oral KRAS G12C inhibitor from Amgen for adults with advanced non-small cell lung cancer or metastatic colorectal cancer that carry the KRAS G12C mutation. It locks the mutant KRAS protein in an inactive state, switching off the growth signal that drives these tumours.
This page is based on FDA and EMA prescribing information for sotorasib (Lumakras / Lumykras), cross-checked with DailyMed, MedlinePlus and the NCI Drug Dictionary; the mechanism is explained in plain language, and analogies are used only where they stay accurate.
How it works
Explains what the medicine does in the body, not dosing, side effects, or safety.
An analogy
KRAS is like a light switch that tells cancer cells to keep growing. In some tumours the switch is jammed in the 'on' position because of a single-letter typo in the gene (G12C). Sotorasib slips a wedge under that switch so it cannot stay on, turning the growth signal off and slowing the cancer down.
In simple terms
Sotorasib targets a specific broken version of the KRAS protein called KRAS G12C, which is found in some lung and colorectal cancers. Normal KRAS acts as a molecular switch that cycles between on and off, but the G12C mutation locks it in the on position, telling cancer cells to grow without stopping. Sotorasib binds to the mutant protein in its inactive form and traps it there, blocking the downstream signals that drive tumour growth. It is taken by mouth and is used only in patients whose tumours carry the KRAS G12C mutation, which must be confirmed by a test before treatment starts.
In depth
Sotorasib (AMG 510) is a small molecule that covalently binds to the switch-II pocket of KRAS G12C when the protein is in its GDP-bound inactive state. The compound exploits a previously unrecognised pocket beneath the effector region, locking KRAS G12C in an inactive conformation and preventing GTP loading and downstream signalling through the RAF-MEK-ERK and PI3K-AKT pathways. Because sotorasib is selective for the G12C variant, it has minimal effect on wild-type KRAS or other KRAS mutants. Resistance can emerge through adaptive feedback reactivation of ERK signalling or through acquisition of secondary KRAS mutations.
See it in motion
A schematic animation of the mechanism — simplified for clarity, not drawn to scale.
KRAS is like a light switch that tells cancer cells to keep growing.
- Sotorasib targets a specific broken version of the KRAS protein called KRAS G12C, which is found in some lung and colorectal cancers.
- Normal KRAS acts as a molecular switch that cycles between on and off, but the G12C mutation locks it in the on position, telling cancer cells to grow without stopping.
- Sotorasib binds to the mutant protein in its inactive form and traps it there, blocking the downstream signals that drive tumour growth.
- It is taken by mouth and is used only in patients whose tumours carry the KRAS G12C mutation, which must be confirmed by a test before treatment starts.
Target: KRAS G12C
A mutant form of the KRAS GTPase that is stuck in its active, GTP-bound state and continuously drives cell growth and survival signals; found in a subset of lung and colorectal cancers.
Approved uses
Approved uses differ by country and change over time. Always follow your local prescribing information.
Approved uses in European Union
EMA- Monotherapy for the treatment of adults with advanced non-small cell lung cancer (NSCLC) with KRAS G12C mutation who have progressed after at least one prior line of systemic therapy
Approved uses in United States
FDA- As a single agent, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy
- In combination with panitumumab, for the treatment of adult patients with KRAS G12C-mutated metastatic colorectal cancer (mCRC), as determined by an FDA-approved test, who have received prior fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy
Approved uses in United States
FDA- As a single agent, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy
- In combination with panitumumab, for the treatment of adult patients with KRAS G12C-mutated metastatic colorectal cancer who have received prior fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy
Approved uses in United States
MedlinePlus- Used to treat certain types of lung cancer (non-small cell lung cancer) and cancer of the colon or rectum
Approved uses in United States
NCI- An orally available inhibitor of the specific KRAS mutation p.G12C with potential antineoplastic activity; selectively targets, binds to and inhibits the activity of the KRAS p.G12C mutant
Official sources
The statements on this page trace back to these records.
- Lumykras (sotorasib) — Summary of product characteristics and package leaflet, English version
European Medicines Agency
- U.S. Food and Drug Administration: LUMAKRAS prescribing information
U.S. Food and Drug Administration
- DailyMed: LUMAKRAS (sotorasib) label
DailyMed, U.S. National Library of Medicine
- MedlinePlus: sotorasib
MedlinePlus, U.S. National Library of Medicine
- National Cancer Institute: sotorasib
National Cancer Institute
This page explains how the medicine works — it isn’t the patient leaflet. For anything that applies to you, read the leaflet that came with your medicine or ask your pharmacist.
MedUnfold provides educational content and is not medical advice. Always follow your local prescribing information and healthcare professional.