Capmatinib
Capmatinib Uses, Dosage, Side Effects, Food Interaction and all others data.
Capmatinib is a small molecule kinase inhibitor targeted against c-Met (a.k.a. hepatocyte growth factor receptor [HGFR]), a receptor tyrosine kinase that, in healthy humans, activates signaling cascades involved in organ regeneration and tissue repair. Aberrant c-Met activation - via mutations, amplification, and/or overexpression - is known to occur in many types of cancer, and leads to overactivation of multiple downstream signaling pathways such as STAT3, PI3K/ATK, and RAS/MAPK. Mutations in MET have been detected in non-small cell lung cancer (NSCLC), and the prevalence of MET amplification in epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-naive patients with NSCLC has been reported to be 1.4% - 21%. This co-occurrence has made c-Met a desirable target in the treatment of NSCLC.
Manufactured by Novartis and marketed under the brand name Tabrecta, capmatinib was granted accelerated approval by the FDA on May 6, 2020, for the treatment of NSCLC in patients whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping. The presence of the mutation must be confirmed by an FDA-approved test, such as the FoundationOne CDx assay (manufactured by Foundation Medicine, Inc.), which was approved by the FDA on the same day. As this indication was granted under an accelerated approval, its continued approval is contingent upon verification of capmatinib's benefit in confirmatory trials.
Capmatinib inhibits the overactivity of c-Met, a receptor tyrosine kinase encoded by the MET proto-oncogene. Mutations in MET are involved in the proliferation of many cancers, including non-small cell lung cancer (NSCLC).
| Trade Name | Capmatinib |
| Availability | Prescription only |
| Generic | Capmatinib |
| Capmatinib Other Names | Capmatinib |
| Related Drugs | Tagrisso, Tarceva, Tabrecta, Gilotrif, Paraplatin, Opdivo, methotrexate, Keytruda, pembrolizumab, cisplatin |
| Weight | 150mg, 200mg |
| Type | Oral tablet |
| Formula | C23H17FN6O |
| Weight | Average: 412.428 Monoisotopic: 412.144787354 |
| Protein binding | Plasma protein binding is approximately 96% and is independent of drug serum concentration. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Capmatinib is a kinase inhibitor targeting c-Met receptor tyrosine kinase in the treatment of non-small cell lung cancer with MET exon 14 skipping.
Capmatinib is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test.
Capmatinib is also used to associated treatment for these conditions: Metastatic Non-Small Cell Lung Cancer
How Capmatinib works
Aberrant activation of c-Met has been documented in many cancers, including non-small cell lung cancer (NSCLC). Mutations that result in the skipping of MET exon 14 lead to the formation of a mutant c-Met with a missing regulatory domain - these mutant proteins have a reduced ability to negatively regulate, leading to a pathological increase in their downstream activity.
Capmatinib inhibits the phosphorylation of both wild-type and mutant variants of c-Met triggered by the binding of its endogenous ligand, hepatocyte growth factor - in doing so, it prevents c-Met-mediated phosphorylation of downstream signaling proteins, as well as the proliferation and survival of c-Met-dependent tumor cells.
Toxicity
Data regarding toxicity and overdose of capmatinib are limited. Embryo-fetal toxicity has been documented in animal models - both males and females using capmatinib should use effective contraception throughout the course of therapy and for 1 week following cessation of therapy.
Food Interaction
- Take with or without food. Co-administration with high-fat meals slightly alters AUC, but not to a clinically significant extent.
Capmatinib Drug Interaction
Moderate: rivaroxabanUnknown: varenicline, bisacodyl, ipratropium, linaclotide, aspirin, cyanocobalamin, cholecalciferol
Capmatinib Disease Interaction
Moderate: liver dysfunction, lung disease, photosensitivity, renal dysfunction
Volume of Distribution
The apparent volume of distribution at steady-state is 164 L.
Elimination Route
The oral bioavailability of capmatinib is estimated to be >70%. Following oral administration, maximum plasma concentrations are achieved within 1 to 2 hours (Tmax). Co-administration with a high-fat meal increased capmatinib AUC by 46% with no change in Cmax (as compared to fasted conditions), and co-administration with a low-fat meal had no clinically meaningful effects on exposure.
Half Life
The elimination half-life is 6.5 hours.
Clearance
The mean apparent clearance of capmatinib at steady-state is 24 L/h.
Elimination Route
Following oral administration of radiolabeled capmatinib, approximately 78% of the radioactivity is recovered in feces, of which ~42% is unchanged parent drug, and 22% is recovered in the urine, of which a negligible amount remains unchanged parent drug.
Innovators Monograph
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