Lumakras
Lumakras Uses, Dosage, Side Effects, Food Interaction and all others data.
Lumakras, also known as AMG-510, is an acrylamide derived KRAS inhibitor developed by Amgen. It is indicated in the treatment of adult patients with KRAS G12C mutant non small cell lung cancer. This mutation makes up >50% of all KRAS mutations. Mutant KRAS discovered in 1982 but was not considered a druggable target until the mid-2010s. It is the first experimental KRAS inhibitor.
The drug MRTX849 is also currently being developed and has the same target.
Lumakras was granted FDA approval on 28 May 2021.
| Trade Name | Lumakras |
| Availability | Prescription only |
| Generic | Sotorasib |
| Sotorasib Other Names | Sotorasib |
| Related Drugs | Lumakras, Opdivo, methotrexate, Keytruda, pembrolizumab, cisplatin, Tagrisso, Avastin |
| Type | Tablets |
| Formula | C30H30F2N6O3 |
| Weight | Average: 560.606 Monoisotopic: 560.234745176 |
| Protein binding | Sotorasib is 89% protein bound in plasma. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States, |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Lumakras is an experimental KRAS inhibitor being investigated for the treatment of KRAS G12C mutant non small cell lung cancer, colorectal cancer, and appendix cancer.
Lumakras is indicated in the treatment of adults with KRAS G12C mutant non small cell lung cancer.
Lumakras is also used to associated treatment for these conditions: Locally Advanced Non-Small Cell Lung Cancer, Metastatic Non-Small Cell Lung Cancer
How Lumakras works
Normally GTP binds to KRAS, activating the protein and promoting effectors to the MAP kinase pathway. GTP is hydrolyzed to GDP, and KRAS is inactivated. KRAS G12C mutations impair hydrolysis of GTP, leaving it in the active form.
Lumakras binds to the cysteine residue in KRAS G12C mutations, holding the protein in its inactive form. The cysteine residue that sotorasib targets is not present in the wild type KRAS, which prevents off-target effects. This mutation is present in 13% of non small cell lung cancer, 3% of colorectal and appendix cancer, and 1-3% of solid tumors.
Toxicity
Data regarding overdoses of sotorasib are not readily available. However, in clinical trials, signs of dose limiting toxicity were not found. Patients experiencing an overdose may experience and increased risk and severity of adverse effects such as diarrhea, nausea, vomiting, fatigue, and elevated aminotransferase.
Food Interaction
- Avoid antacids. If coadministration cannot be avoided, take sotorasib 4 hours before or 10 hours after antacids.
- Take with or without food. Taking sotorasib with a high fat, high calorie meal increases total exposure to sotorasib by 25%.
[Minor] Food does not appear to have a clinically significant effect on the oral bioavailability of sotorasib.
When a 960 mg dose of sotorasib was administered to study patients with a high-fat, high-calorie meal (approximately 800 to 1000 calories; 150, 250, and 500 to 600 calories from protein, carbohydrate, and fat, respectively), sotorasib peak plasma concentration (Cmax) did not change while systemic exposure (AUC 0-24 hours) increased by 25% compared to administration under fasted conditions.
Lumakras can be administered with or without food at approximately the same time each day.
Volume of Distribution
The volume of distribution of sotorasib is 211 L.
Elimination Route
A 960 mg once daily dose of sotorasib reaches a Cmax of 7.50 µg/mL, with a median Tmax of 2.0 hours, and an AUC0-24h of 65.3 h*µg/mL.
Half Life
Lumakras has a terminal elimination half life of 5.5 ± 1.8 hours.
Clearance
Lumakras has an apparent clearance at steady state of 26.2 L/h.
Elimination Route
Lumakras is 74% eliminated in the feces and 6% eliminated in the urine. 53% of the dose recovered in the feces and 1% of the dose recovered in the urine is in the form of the unchanged parent compound.
Innovators Monograph
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