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'''Capmatinib''', sold under the brand name '''Tabrecta''', is a medication 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.
'''Capmatinib''', sold under the brand name '''Tabrecta''', is a medication 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.<ref name="Tabrecta FDA label">{{cite web | title=Tabrecta- capmatinib tablet, film coated | website=DailyMed | date=6 May 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=455892c3-d144-4ba8-9ab4-79cabff9876d | access-date=8 May 2020}}</ref><ref name="FDA PR">{{cite press release | title=FDA Approves First Targeted Therapy to Treat Aggressive Form of Lung Cancer | website=U.S. [[Food and Drug Administration]] (FDA) | date=6 May 2020 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-therapy-treat-aggressive-form-lung-cancer | access-date=8 May 2020}} {{PD-notice}}</ref>


The most common adverse reactions are peripheral [[edema]], nausea, fatigue, vomiting, [[dyspnea]], and decreased appetite.<ref name="FDA capmatinib" />
The most common adverse reactions are peripheral [[edema]], nausea, fatigue, vomiting, [[dyspnea]], and decreased appetite.<ref name="Tabrecta FDA label" /><ref name="FDA capmatinib" /><ref name="FDA PR" />

Non-small cell lung cancer (NSCLC) is a disease in which malignant cancer cells form in the tissues of the lung.<ref name="FDA PR" /> It is the most common type of lung cancer with up to 90% of all lung carcinomas falling into the non-small cell category.<ref name="FDA PR" /> NSCLC occurs when healthy cells become abnormal and grow rapidly.<ref name="FDA PR" /> One danger of this form of cancer is that there's a high likelihood that the cancer cells will spread from the lungs to other organs and body parts.<ref name="FDA PR" /> Cancer metastasis consists of a sequential series of events, and MET exon 14 skipping is recognized as a critical event for metastasis of carcinomas.<ref name="FDA PR" /> Mutations leading to MET exon 14 skipping are found in 3-4% of patients with lung cancer.<ref name="FDA PR" />

Capmatinib 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).<ref name="FDA PR" />


== Medical uses ==
== 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.<ref name="FDA capmatinib" />
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.<ref name="Tabrecta FDA label" /><ref name="FDA capmatinib" />


== Adverse effects ==
== Adverse effects ==
Capmatinib can cause interstitial lung disease, hepatotoxicity, photosensitivity, and embryo-fetal toxicity.<ref name="FDA capmatinib" /> 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.<ref name="FDA capmatinib" />
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.<ref name="FDA capmatinib" /> 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.<ref name="FDA capmatinib" /><ref name="FDA PR" />

Capmatinib may cause harm to a developing fetus or newborn baby.<ref name="Tabrecta FDA label" /><ref name="FDA PR" />


==Pharmacology==
==Pharmacology==
Line 122: Line 128:
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.<ref name="FDA capmatinib">{{cite web | title=FDA grants accelerated approval to capmatinib for metastatic non-small | website=U.S. [[Food and Drug Administration]] (FDA) | date=6 May 2020 | url=https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-capmatinib-metastatic-non-small-cell-lung-cancer | access-date=6 May 2020}} {{PD-notice}}</ref><ref>{{cite web | title=Tabrecta: FDA-Approved Drugs | website=U.S. [[Food and Drug Administration]] (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=213591 | access-date=6 May 2020}}</ref>
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.<ref name="FDA capmatinib">{{cite web | title=FDA grants accelerated approval to capmatinib for metastatic non-small | website=U.S. [[Food and Drug Administration]] (FDA) | date=6 May 2020 | url=https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-capmatinib-metastatic-non-small-cell-lung-cancer | access-date=6 May 2020}} {{PD-notice}}</ref><ref>{{cite web | title=Tabrecta: FDA-Approved Drugs | website=U.S. [[Food and Drug Administration]] (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=213591 | access-date=6 May 2020}}</ref>


Efficacy was demonstrated in the GEOMETRY mono-1 trial (NCT02414139), a multicenter, non-randomized, open-label, multicohort study enrolling 97 participants with metastatic NSCLC with confirmed MET exon 14 skipping.<ref name="FDA capmatinib" /> Participants received capmatinib 400 mg orally twice daily until disease progression or unacceptable toxicity.<ref name="FDA capmatinib" />
Efficacy was demonstrated in the GEOMETRY mono-1 trial (NCT02414139), a multicenter, non-randomized, open-label, multicohort study enrolling 97 participants with metastatic NSCLC with confirmed MET exon 14 skipping.<ref name="FDA capmatinib" /> Participants received capmatinib 400 mg orally twice daily until disease progression or unacceptable toxicity.<ref name="FDA capmatinib" /><ref name="FDA PR" />

The major efficacy outcome measure was overall response rate (ORR), which reflects the percentage of participants that had a certain amount of tumor shrinkage.<ref name="FDA PR" /> An additional efficacy outcome measure was duration of response (DOR).<ref name="FDA PR" /> The efficacy population included 28 patients who had never undergone treatment for NSCLC and 69 previously treated patients.<ref name="FDA PR" /> The ORR for the 28 participants was 68%, with 4% having a complete response and 64% having a partial response.<ref name="FDA PR" /> The ORR for the 69 participants was 41%, with all having a partial response.<ref name="FDA PR" /> 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.<ref name="FDA PR" />


The U.S. [[Food and Drug Administration]] (FDA) granted the application for capmatinib [[orphan drug]] and [[breakthrough therapy]] designations<ref name="FDA capmatinib" /> and granted the approval of Tabrecta to Novartis.<ref name="FDA capmatinib" />
The US [[Food and Drug Administration]] (FDA) granted the application for capmatinib [[priority review]], [[orphan drug]], and [[breakthrough therapy]] designations<ref name="FDA capmatinib" /><ref name="FDA PR" /> and granted the approval of Tabrecta to Novartis Pharmaceuticals Corporation.<ref name="FDA capmatinib" /><ref name="FDA PR" />


== References ==
== References ==

Revision as of 23:40, 8 May 2020

Capmatinib
Clinical data
Trade namesTabrecta
Other namesINC280
License data
Routes of
administration		By mouth
ATC code
  • none
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.246.414 Edit this at Wikidata
Chemical and physical data
FormulaC23H17FN6O
Molar mass412.428 g·mol−1
3D model (JSmol)
  • CNC(=O)C1=C(C=C(C=C1)C2=NN3C(=CN=C3N=C2)CC4=CC5=C(C=C4)N=CC=C5)F
  • 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 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.[1][2]

The most common adverse reactions are peripheral edema, nausea, fatigue, vomiting, dyspnea, and decreased appetite.[1][3][2]

Non-small cell lung cancer (NSCLC) is a disease in which malignant cancer cells form in the tissues of the lung.[2] It is the most common type of lung cancer with up to 90% of all lung carcinomas falling into the non-small cell category.[2] NSCLC occurs when healthy cells become abnormal and grow rapidly.[2] One danger of this form of cancer is that there's a high likelihood that the cancer cells will spread from the lungs to other organs and body parts.[2] Cancer metastasis consists of a sequential series of events, and MET exon 14 skipping is recognized as a critical event for metastasis of carcinomas.[2] Mutations leading to MET exon 14 skipping are found in 3-4% of patients with lung cancer.[2]

Capmatinib 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).[2]

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.[1][3]

Adverse 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.[3] 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.[3][2]

Capmatinib may cause harm to a developing fetus or newborn baby.[1][2]

Pharmacology

The substance inhibits c-Met,[4][5] 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.[3][6]

Efficacy was demonstrated in the GEOMETRY mono-1 trial (NCT02414139), a multicenter, non-randomized, open-label, multicohort study enrolling 97 participants with metastatic NSCLC with confirmed MET exon 14 skipping.[3] Participants received capmatinib 400 mg orally twice daily until disease progression or unacceptable toxicity.[3][2]

The major efficacy outcome measure was overall response rate (ORR), which reflects the percentage of participants that had a certain amount of tumor shrinkage.[2] An additional efficacy outcome measure was duration of response (DOR).[2] The efficacy population included 28 patients who had never undergone treatment for NSCLC and 69 previously treated patients.[2] The ORR for the 28 participants was 68%, with 4% having a complete response and 64% having a partial response.[2] The ORR for the 69 participants was 41%, with all having a partial response.[2] 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.[2]

The US Food and Drug Administration (FDA) granted the application for capmatinib priority review, orphan drug, and breakthrough therapy designations[3][2] and granted the approval of Tabrecta to Novartis Pharmaceuticals Corporation.[3][2]

References

  1. ^ a b c d "Tabrecta- capmatinib tablet, film coated". DailyMed. 6 May 2020. Retrieved 8 May 2020.
  2. ^ a b c d e f g h i j k l m n o p q r s t "FDA Approves First Targeted Therapy to Treat Aggressive Form of Lung Cancer". U.S. Food and Drug Administration (FDA) (Press release). 6 May 2020. Retrieved 8 May 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  3. ^ a b c d e f g h i "FDA grants accelerated approval to capmatinib for metastatic non-small". U.S. Food and Drug Administration (FDA). 6 May 2020. Retrieved 6 May 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  4. ^ 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.
  5. ^ 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.
  6. ^ "Tabrecta: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 6 May 2020.

External links

  • "Capmatinib". Drug Information Portal. U.S. National Library of Medicine.
  • Clinical trial number NCT02414139 for "Clinical Study of Oral cMET Inhibitor INC280 in Adult Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer" at ClinicalTrials.gov
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