Capmatinib

Capmatinib
Names
Trade namesTabrecta
Other namesINC280
Clinical data
Drug classTyrosine kinase inhibitor[1]
Main usesNon-small cell lung cancer (NSCLC)[2]
Side effectsPeripheral swelling, nausea, tiredness, shortness of breath, decreased appetite[2]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • Not recommended
Routes of
use		By mouth
Typical dose400 mg BID[2]
External links
AHFS/Drugs.comMonograph
MedlinePlusa620038
Legal
License data
Legal status
Chemical and physical data
FormulaC23H17FN6O
Molar mass412.428 g·mol−1
3D model (JSmol)
SMILES
  • CNC(=O)C1=C(C=C(C=C1)C2=NN3C(=CN=C3N=C2)CC4=CC5=C(C=C4)N=CC=C5)F
InChI
  • InChI=1S/C23H17FN6O/c1-25-22(31)18-6-5-16(11-19(18)24)21-13-28-23-27-12-17(30(23)29-21)10-14-4-7-20-15(9-14)3-2-8-26-20/h2-9,11-13H,10H2,1H3,(H,25,31)
  • Key:LIOLIMKSCNQPLV-UHFFFAOYSA-N

Capmatinib, sold under the brand name Tabrecta, is a medication used to treat non-small cell lung cancer (NSCLC).[2] Specifically it is used for metastatic disease with MET exon 14 skipping.[2] This is found in 3-4% of people with lung cancer.[3] It is taken by mouth.[2]

Common side effects include peripheral swelling, nausea, tiredness, shortness of breath, and decreased appetite.[2] Other side effects may include pneumonitis, liver problems, and sunburns.[2] Use during pregnancy may harm the baby.[2] It is a tyrosine kinase inhibitor.[1]

Capmatinib was approved for medical use in the United States in 2020.[1] It is not approved in Europe or the United Kingdom as of 2021.[4] In the United States 4 weeks costs about 19,800 USD as of 2021.[5]

Medical uses

Capmatinib is a kinase inhibitor indicated for the treatment of adults 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.[2][6]

Dosage

It is used at a dose of 400 mg twice per day.[2]

Side effects

Capmatinib can cause interstitial lung disease (a group of lung conditions that causes scarring of lung tissues), pneumonitis (inflammation of the lung tissue), hepatotoxicity (damage to liver cells), photosensitivity, and embryo-fetal toxicity.[6] Based on a clear positive signal for phototoxicity in early laboratory studies in cells, people may be more sensitive to sunlight and should be advised to take precautions to cover their skin, use sunscreen, and not tan while taking capmatinib.[6][3]

Capmatinib may cause harm to a developing fetus or newborn baby.[2][3]

Pharmacology

The substance inhibits c-Met,[7][8] a tyrosine kinase that plays a role in embryonic development, organogenesis and wound healing, but also in the development of cancer.

History

Capmatinib was approved for medical use in the United States in May 2020, along with the FoundationOne CDx assay as a companion diagnostic for capmatinib.[6][9]

Efficacy was demonstrated in the GEOMETRY mono-1 trial (NCT02414139), a multicenter, non-randomized, open-label, multicohort study enrolling 334 participants with metastatic NSCLC with confirmed MET exon 14 skipping.[10][6] Some participants were previously treated for their cancer and some were not (treatment-naïve).[10] Participants received capmatinib 400 mg orally twice daily until disease progression or unacceptable toxicity.[6][3] The efficacy was based on results from 97 of the participants.[10] The trial was conducted at 92 sites in the United States, Austria, Belgium, France, Germany, Israel, Italy, Japan, Korea, Lebanon, Mexico, Netherlands, Norway, Russia, Singapore, Sweden, Switzerland, Spain, Taiwan and the UK.[10]

The major efficacy outcome measure was overall response rate (ORR), which reflects the percentage of participants that had a certain amount of tumor shrinkage.[3] An additional efficacy outcome measure was duration of response (DOR).[3] The efficacy population included 28 participants who had never undergone treatment for NSCLC and 69 previously treated participants.[3] The ORR for the 28 participants was 68%, with 4% having a complete response and 64% having a partial response.[3] The ORR for the 69 participants was 41%, with all having a partial response.[3] Of the responding participants who had never undergone treatment for NSCLC, 47% had a duration of response lasting 12 months or longer compared to 32.1% of the responding participants who had been previously treated.[3]

The US Food and Drug Administration (FDA) processed the application under the accelerated approval program and granted the application for capmatinib priority review, orphan drug, and breakthrough therapy designations[6][3] and granted the approval of Tabrecta to Novartis Pharmaceuticals Corporation.[6][3]

It is the first therapy approved by the US Food and Drug Administration (FDA) to treat non-small cell lung cancer with specific mutations (those that lead to mesenchymal-epithelial transition or MET exon 14 skipping).[3]

References

  1. 1 2 3 "Capmatinib Monograph for Professionals". Drugs.com. Retrieved 29 December 2021.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 "Tabrecta- capmatinib tablet, film coated". DailyMed. 6 May 2020. Archived from the original on 8 May 2020. Retrieved 8 May 2020.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 "FDA Approves First Targeted Therapy to Treat Aggressive Form of Lung Cancer". U.S. Food and Drug Administration (FDA) (Press release). 6 May 2020. Archived from the original on 7 May 2020. Retrieved 8 May 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  4. ↑ "Capmatinib". SPS - Specialist Pharmacy Service. 4 July 2020. Archived from the original on 14 August 2020. Retrieved 29 December 2021.
  5. ↑ "Tabrecta Prices, Coupons & Patient Assistance Programs". Drugs.com. Retrieved 29 December 2021.
  6. 1 2 3 4 5 6 7 8 "FDA grants accelerated approval to capmatinib for metastatic non-small". U.S. Food and Drug Administration (FDA). 6 May 2020. Archived from the original on 7 May 2020. Retrieved 6 May 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  7. ↑ Shaker ME, Shaaban AA, El-Shafey MM, El-Mesery ME (April 2020). "The selective c-Met inhibitor capmatinib offsets cisplatin-nephrotoxicity and doxorubicin-cardiotoxicity and improves their anticancer efficacies". Toxicology and Applied Pharmacology. 398: 115018. doi:10.1016/j.taap.2020.115018. PMID 32333917.
  8. ↑ Qin S, Chan SL, Sukeepaisarnjaroen W, Han G, Choo SP, Sriuranpong V, et al. (2019). "A phase II study of the efficacy and safety of the MET inhibitor capmatinib (INC280) in patients with advanced hepatocellular carcinoma". Therapeutic Advances in Medical Oncology. 11: 1758835919889001. doi:10.1177/1758835919889001. PMC 6906348. PMID 31853265.
  9. ↑ "Tabrecta: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on 6 May 2020. Retrieved 6 May 2020.
  10. 1 2 3 4 "Drug Trials Snapshots: Tabrecta". U.S. Food and Drug Administration (FDA). 6 May 2020. Archived from the original on 8 August 2020. Retrieved 21 May 2020. Public Domain This article incorporates text from this source, which is in the public domain.
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