Mobocertinib, sold under the brand name Exkivity, is used for the treatment of

non-small cell lung cancer Non-small-cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to sm ...

. The most common side effects include diarrhea,

rash A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cr ...

, nausea,

stomatitis Stomatitis is inflammation of the mouth and lips. It refers to any inflammatory process affecting the mucous membranes of the mouth and lips, with or without oral ulceration. In its widest meaning, stomatitis can have a multitude of different cau ...

, vomiting, decreased appetite,

paronychia Paronychia is an inflammation of the skin around the nail, which can occur suddenly, when it is usually due to the bacterium '' Staphylococcus aureus'', or gradually when it is commonly caused by the fungus ''Candida albicans''. The term is fr ...

fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

, dry skin, and musculoskeletal pain. Mobocertinib is a small molecule

tyrosine kinase A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions. Tyrosine kinases belong to a larger cla ...

inhibitor. Its molecular target is

epidermal growth factor receptor The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands. The epidermal growth factor recept ...

(EGFR) bearing mutations in the

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...

20 region. Mobocertinib is an irreversible kinase inhibitor, forming a covalent bond with the cysteine 797 in the EGFR active site, leading to sustained inhibition of EGFR enzymatic activity. The irreversible binding leads to increased potency via higher affinity binding, more sustained EGFR kinase activity inhibition, and greater overall selectivity, as only a limited number of other kinases possess a cysteine in the equivalent position. Mobocertinib was approved for medical use in the United States in September 2021. It is a first-in-class oral treatment to target EGFR Exon20 insertion mutations.

Medical uses

Mobocertinib is indicated for adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after

platinum-based chemotherapy Platinum-based antineoplastic drugs (informally called platins) are chemotherapeutic agents used to treat cancer. They are coordination complexes of platinum. These drugs are used to treat almost half of people receiving chemotherapy for cancer. I ...

Mechanism of action

Mobocertinib acts to inhibit EGFR exon 20 insertion mutations at a lower concentration than it does on wild-type proteins.

Pharmacokinetics

The volume of distribution of Mobocertinib at steady state is 3,509 L. The mean oral bioavailability of Mobocertinib is 37%. The median Tmax is 4 hours. The average half-life of Mobocertinib and its metabolites is 18 hours. Mobocertinib is metabolized by CYP3A enzymes.

Warnings

Mobocertinib may increase the chance of QTC prolongation, specifically Torsades de Pointes which can be fatal.

Adverse Effects

More serious side effects of Mobocertinib may include agitation, bloating of the eyes, lips, feet, blurred vision, coma, decreased urine output, headache, hostility, diarrhea, depression, dizziness, fainting, lethargy, anxiety, nausea, seizures, weight gain, fatigue as well as edema. Other side effects which may be less frequent are: chills, cough, dilated neck veins, ill-feeling and trouble with breathing. Other notable side effects of taking Mobocertinib are: having an acidic stomach, heartburn, acidity, hair loss/thinning, bone pain, sore throat, stuffy nose, trouble swallowing, vomiting and weakness in hands and feet.

History

Mobocertinib was studied in participants with previously treated metastatic non-small cell lung cancer with EGFR exon 20 insertions. The FDA granted the application for mobocertinib

orphan drug An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

designation.

References

External links

* * Amides Breakthrough therapy CYP3A4 inducers Dimethylamino compounds Indoles Isopropyl esters Kinase inhibitors Orphan drugs Pyrimidines Tertiary amines {{antineoplastic-drug-stub