Product Name: LuciMob

Chinese Name: Mobocertinib

English Name: Mobocertinib

[Summary]

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

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

In cultured cell models, Mobocertinib inhibits cell proliferation driven by various EGFR exon 20 insertion mutation variants at concentrations 1.5 to 10 times lower than those required to inhibit WT-EGFR signaling.

In animal tumor xenograft models, Mobocertinib demonstrated anti-tumor activity against xenografts harboring EGFR exon 20 insertion mutations (NPH or ASV).

[Indications]

Mobocertinib is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring 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.

[Specification]

40 mg/capsule; 120 capsules/box.

[Storage]

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). [Dosage and Administration]

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

[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 are lymphopenia, increased amylase, increased lipase, hypokalemia, decreased hemoglobin, increased creatinine, and hypomagnesemia.

[Contraindications]

None.

[Warnings and Precautions]

LuciMob can cause life-threatening corrected QT (QTc) interval prolongation, including Torsades de Pointes, which may be fatal; QTc monitoring and periodic electrolyte assessments are required at baseline and during treatment.

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

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

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

Interstitial Lung Disease (ILD)/Pneumonitis: Monitor patients for new or worsening pulmonary symptoms suggestive of ILD/pneumonitis. Immediately withhold LuciMob in patients with suspected ILD/pneumonitis; permanently discontinue LuciMob if ILD/pneumonitis is confirmed.

Cardiotoxicity: Monitor cardiac function, including left ventricular ejection fraction, at baseline and during treatment. Withhold, reduce the dose upon recovery, or permanently discontinue the drug based on severity.

Diarrhea: Diarrhea may lead to dehydration or electrolyte imbalance, with or without renal impairment. Monitor electrolytes and advise patients to initiate antidiarrheal agents and increase fluid and electrolyte intake at the first onset of diarrhea. Withhold, reduce the dose, or permanently discontinue LuciMob based on severity.

Embryo-Fetal Toxicity: May cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective non-hormonal contraception. [Safety and Efficacy]

Mobocertinib is the first oral therapy approved in the United States specifically targeting EGFR Exon 20 insertion mutations. The U.S. FDA approval was based on data from a Phase 1/2 clinical trial involving a patient population that had previously received platinum-based chemotherapy.

Data presented at the 2021 ASCO Annual Meeting demonstrated that, based on assessments by an Independent Data Monitoring Committee, patients treated with Mobocertinib (160 mg) once daily achieved an objective response rate (ORR) of 28% (35% per investigator assessment), a median duration of response (mDoR) of 17.5 months, a median progression-free survival (mPFS) of 7.3 months, and a disease control rate of 78%.