Exkivity

Introduction to mobocertinib

Common name: mobocertinib

Trade name (English): Exkivity

Trade name (Chinese): Anweili

Full names: Mobocertinib succinate capsules, Mobocertinib, Exkivity, TAK-788, mobo certinib

INDICATIONS:

EXKIVITY is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, whose disease has progressed during or after platinum-based chemotherapy, as detected by an FDA-approved test.

Usage and Dosage:

Recommended dose: 160 mg orally once daily, with or without food.

Specification:

40mg

Adverse reactions:

The most common (>20%) adverse reactions are diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin and musculoskeletal pain.

The most common (≥2%) grade 3 or 4 laboratory abnormalities were lymphopenia, increased lymphocyte amylase, increased lipase, decreased potassium, decreased hemoglobin, increased creatinine, and decreased magnesium.

Contraindications:

None

Precautions:

EXKIVITY can cause life-threatening rate-corrected QT (QTc) prolongation, including torsade de pointes, which may be fatal and requires monitoring of QTc and periodic electrolyte checks at baseline and during treatment.

Increase the frequency of monitoring in patients with risk factors for QTc prolongation.

Avoid the use of concomitant drugs known to prolong the QTc interval, as well as the use of strong or moderate CYP3A inhibitors with EXKIVITY, which may further prolong the QTc.

Withhold, reduce dose, or permanently discontinue EXKIVITY based on severity of QTc prolongation.

Interstitial Lung Disease (ILD)/Pneumonitis: Monitor patients for new or worsening pulmonary symptoms suggestive of ILD/pneumonitis. Discontinue EXKIVITY immediately in patients with suspected ILD/pneumonitis and permanently discontinue EXKIVITY if ILD/pneumonitis is confirmed.

Cardiotoxicity: Monitor cardiac function, including left ventricular ejection fraction, at baseline and during treatment. Withhold, resume at reduced dose, or permanently discontinue depending on severity.

Diarrhea: Diarrhea may lead to dehydration or electrolyte imbalance, with or without kidney damage. Monitor electrolytes and advise patients to start antidiarrheal medications and increase fluid and electrolyte intake at the first episode of diarrhea. Withhold, reduce dose, or permanently discontinue EXKIVITY based on severity.

Embryo-fetal toxicity: May cause harm to the fetus. Advise women of childbearing potential of the potential risks to the fetus and to use effective non-hormonal contraceptives.

Storage:

The most common (>20%) adverse reactions are diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain. The most common (≥2%) grade 3 or 4 laboratory abnormalities were lymphopenia, increased amylase, increased lipase, decreased potassium, decreased hemoglobin, increased creatinine, and decreased magnesium.

Mechanism of action:

Mobocertinib is an epidermal growth factor receptor (EGFR) kinase inhibitor that irreversibly binds to and inhibits EGFR exon 20 insertion mutations at lower concentrations than wild-type (WT) EGFR. Two pharmacologically active metabolites (AP32960 and AP32914) with similar inhibitory properties to mobocertinib have been found in plasma following oral administration of mobocertinib.

In vitro, mobocertinib also inhibits the activity of other EGFR family members (HER2 and HER4) and an additional kinase (BLK) at clinically relevant concentrations (IC50 values ​​<2nM).

In cultured cell models, mobocertinib inhibited cell proliferation driven by different EGFR exon 20 insertion mutant variants at concentrations 1.5- to 10-fold lower than inhibition of WT-EGFR signaling.

In animal tumor implantation models, mobocertinib demonstrated antitumor activity against xenografts containing EGFR exon 20 insertions of NPH or ASV.

Safety and efficacy:

Mobocertinib is the first oral therapy approved in the United States for EGFR Exon20 insertion mutations. The US FDA's approval was based on a patient population who had received platinum-containing chemotherapy in a phase 1/2 clinical trial.

Data announced at the 2021 ASCO Annual Meeting showed that according to the evaluation of the independent data monitoring center, the objective response rate of patients receiving mobocertinib (160mg) once daily treatment was 28% (investigator evaluation was 35%), the median duration of response (mDoR) was 17.5 months, the median progression-free survival (mPFS) was 7.3 months, and the disease control rate was 78%.

For complete instructions, please see: https://content.takeda.com/?contenttype=pi&product=

exkivity&language=eng&country=usa&documentnumber=1