Introduction of Mobocertinib

Mobocertinib is the world’s first targeted therapy specifically designed for the treatment of advanced non‑small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations (EGFR ex20ins), addressing a critical unmet medical need for this difficult‑to‑treat subtype.

Indications

This product is 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, whose disease has progressed during or after prior platinum‑containing chemotherapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Overview

Dosage and Administration

Patient Selection

Presence of EGFR exon 20 insertion mutation must be confirmed by an FDA‑approved test.

Recommended Dosage

160mg orally once daily, with or without food.

Treatment should be continued until disease progression or unacceptable toxicity.

Administration

Swallow capsules whole. Do not open, chew, or dissolve the capsule contents.

Missed Dose

If a dose is missed by more than 6 hours, skip the missed dose and take the next dose at the usual time the next day.

Vomiting

If vomiting occurs after administration, do not take an additional dose. Take the next dose at the usual time the next day.

Dosage Modification

Adverse Reactions

Dosing may need to be interrupted, reduced, or permanently discontinued based on severity of adverse reactions.

Dose reduction levels

First reduction: 120mg once daily.

Second reduction: 80mg once daily.

Concomitant Use with Moderate CYP3A Inhibitors

If co‑administration cannot be avoided, reduce the dose by approximately 50% (e.g., from 160mg to 80mg).

Severe Renal Impairment

Dose reduction by approximately 50% is recommended (e.g., from 160mg to 80mg).

Use in Specific Populations

Pregnancy

Based on animal studies, may cause fetal harm.

Advise females of reproductive potential to use effective non‑hormonal contraception during treatment and for 1 month after the last dose.

Lactation

Advise not to breastfeed during treatment and for 1 week after the last dose.

Females and Males of Reproductive Potential

Females

Verify pregnancy status prior to treatment.

Use effective non‑hormonal contraception during treatment and for 1 month after the last dose.

This product may render hormonal contraceptives ineffective.

Males

Use effective contraception during treatment and for 1 week after the last dose when partnering with females of reproductive potential.

Infertility

May impair male and female fertility.

Pediatric Patients

Safety and effectiveness in pediatric patients have not been established.

Geriatric Patients

Patients aged 65 years and older have a higher incidence of Grade 3–4 adverse reactions and serious adverse reactions compared with younger patients.

Renal Impairment

Severe (eGFR <30 mL/min/1.73m²): Dose reduction required.

Mild to moderate (eGFR 30–89 mL/min/1.73m²): No dose adjustment needed.

Hepatic Impairment

No dose adjustment is required in patients with mild to severe hepatic impairment.

Adverse Reactions

Serious Side Effects (Seek Medical Attention Immediately)

QTc Prolongation and Torsades de Pointes (Boxed Warning)

May cause life‑threatening arrhythmias or death.

Symptoms include dizziness, lightheadedness, and syncope.

Monitor ECG and electrolytes at baseline and periodically during treatment.

Interstitial Lung Disease (ILD)/Pneumonitis

May be fatal.

Promptly seek medical care for new or worsening pulmonary symptoms (cough, shortness of breath, chest pain).

Cardiac Toxicity

Including heart failure, decreased ejection fraction.

Symptoms: palpitations, dyspnea, chest pain, edema, syncope.

Diarrhea

Very common (93%), may be severe and lead to dehydration or electrolyte imbalance.

Initiate antidiarrheal treatment (e.g., loperamide) at first onset of loose stools or increased bowel frequency, and increase fluid and electrolyte intake.

Most Common Adverse Reactions (≥20%)

Diarrhea, rash, stomatitis, vomiting, decreased appetite, paronychia, nausea, musculoskeletal pain, dry skin, fatigue, cough, pruritus, weight decreased.

Most Common Grade 3 or 4 Laboratory Abnormalities (≥2%)

Lymphopenia, increased amylase, increased lipase, decreased potassium, decreased hemoglobin, increased creatinine, decreased magnesium, increased alanine aminotransferase (ALT).

Contraindications

None.

Warnings and Precautions

QTc Prolongation and Torsades de Pointes (Boxed Warning)

Assess QTc interval and electrolytes (sodium, potassium, calcium, magnesium) before treatment and correct abnormalities.

Avoid concomitant use with drugs known to prolong QTc interval.

Avoid concomitant use with strong or moderate CYP3A inhibitors (may further prolong QTc).

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

Interstitial Lung Disease (ILD)/Pneumonitis

Immediately withhold treatment in patients with suspected ILD/pneumonitis; permanently discontinue if confirmed.

Cardiac Toxicity

Monitor cardiac function (including left ventricular ejection fraction) at baseline and during treatment.

Interrupt, reduce dose, or permanently discontinue based on severity.

Diarrhea

Monitor electrolytes.

Interrupt, reduce dose, or permanently discontinue based on severity.

Embryo‑Fetal Toxicity

See Use in Specific Populations.

Drug Interactions

Strong/Moderate CYP3A Inhibitors

Avoid co‑administration. If co‑administration with moderate inhibitors cannot be avoided, reduce dose and monitor QTc more frequently.

Strong/Moderate CYP3A Inducers

Avoid co‑administration; may decrease efficacy.

CYP3A Substrates

This product may decrease their efficacy. Avoid co‑administration with hormonal contraceptives.

Monitoring Recommendations

Periodically monitor ECG, electrolytes, cardiac function, and new or worsening pulmonary symptoms during treatment.

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