Usual Adult Dose for Non-Small Cell Lung Cancer

160 mg orally once a day
Duration of therapy: Until disease progression or unacceptable toxicity

Use: For the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations (as detected by a US FDA-approved test) whose disease has progressed on or after platinum-based chemotherapy

Renal Dose Adjustments

Mild to moderate renal dysfunction (estimated GFR 30 to 89 mL/min/1.73 m2): No adjustment recommended.
Severe renal dysfunction (estimated GFR less than 30 mL/min/1.73 m2): Data not available

Comments:

• Estimated GFR 30 to 89 mL/min/1.73 m2 by Modification of Diet in Renal Disease equation
• The recommended dosage has not been established for patients with severe renal dysfunction.

Liver Dose Adjustments

Mild or moderate liver dysfunction: No adjustment recommended.
Severe liver dysfunction: Data not available

Comments:

• Mild liver dysfunction: Total bilirubin up to the upper limit of normal (ULN) and AST greater than ULN or total bilirubin greater than 1 to 1.5 times ULN (1 to 1.5 x ULN) and any AST
• Moderate liver dysfunction: Total bilirubin 1.5 to 3 x ULN and any AST
• Severe liver dysfunction: Total bilirubin greater than 3 x ULN and any AST
• The recommended dosage has not been established for patients with severe liver dysfunction.

Dose Adjustments

Dose reduction levels for adverse reactions:

• First dose reduction: 120 mg orally once a day
• Second dose reduction: 80 mg orally once a day

• Grade 2 (QTc interval 481 to 500 msec):
• First occurrence: This drug should be withheld until Grade 1 or lower or baseline; upon recovery, this drug should resume at the same dose.
• Recurrence: This drug should be withheld until Grade 1 or lower or baseline; upon recovery, this drug should resume at the next lower dose or should be permanently discontinued.
• Grade 3 (QTc interval at least 501 msec or QTc interval increase of greater than 60 msec from baseline):
• First occurrence: This drug should be withheld until Grade 1 or lower or baseline; upon recovery, this drug should resume at the next lower dose or should be permanently discontinued.
• Recurrence: This drug should be permanently discontinued.
• Grade 4 (torsades de pointes; polymorphic ventricular tachycardia; signs/symptoms of serious arrhythmia): This drug should be permanently discontinued.

• Any grade: This drug should be withheld if ILD/pneumonitis is suspected; if ILD/pneumonitis is confirmed, this drug should be permanently discontinued.

• Grade 2 decreased ejection fraction: This drug should be withheld until Grade 1 or lower or baseline.
• If recovered to baseline within 2 weeks: This drug should resume at the same dose or the next lower dose.
• If not recovered to baseline within 2 weeks: This drug should be permanently discontinued.
• At least Grade 2 heart failure or Grade 3 or 4 decreased ejection fraction: This drug should be permanently discontinued.

• Intolerable or recurrent Grade 2 or Grade 3: This drug should be withheld until Grade 1 or lower; this drug should resume at the same dose or the next lower dose.
• Grade 4:
• First occurrence: This drug should be withheld until Grade 1 or lower; this drug should resume at the next lower dose.
• Recurrence: This drug should be permanently discontinued.

• Intolerable or recurrent Grade 2 or Grade 3: This drug should be withheld until Grade 1 or lower; this drug should resume at the same dose or the next lower dose.
• Grade 4:
• First occurrence: This drug should be withheld until Grade 1 or lower.
• If recovery occurs within 2 weeks: This drug should resume at the next lower dose.
• If recovery does not occur within 2 weeks: This drug should be permanently discontinued.
• Recurrence: This drug should be permanently discontinued.

• If coadministration cannot be avoided: The mobocertinib dose should be reduced by about 50% (i.e., from 160 to 80 mg, 120 to 40 mg, or 80 to 40 mg) and QTc interval should be monitored more frequently.
• After the moderate CYP450 3A inhibitor has been discontinued for 3 to 5 elimination half-lives: Mobocertinib should resume at the dose taken before starting the moderate CYP450 3A inhibitor.

Precautions

US BOXED WARNING:

• QTc PROLONGATION AND TORSADES DE POINTES: This drug can cause life-threatening QTc prolongation, including torsades de pointes (which can be fatal), and requires monitoring of QTc and electrolytes at baseline and periodically during therapy; monitoring frequency should be increased in patients with risk factors for QTc prolongation. Use of concomitant drugs known to prolong the QTc interval and use of strong or moderate CYP450 3A inhibitors should be avoided with this drug, which may further prolong the QTc. Therapy should be withheld, the dose should be reduced, or this drug should be permanently discontinued based on the severity of QTc prolongation.

Dialysis

Data not available

Other Comments

Administration advice:

• Select patients with locally advanced/metastatic NSCLC for treatment with this drug based on the presence of EGFR exon 20 insertion mutations.
• For information on US FDA-approved tests: fda.gov/CompanionDiagnostics
• Administer with or without food, at the same time each day.
• Swallow capsules whole; do not open, chew, or dissolve the contents of the capsules.
• If a dose is vomited, do not administer an additional dose; administer the next dose as prescribed the following day.

• Store at 20C to 25C (68F to 77F); excursions permitted from 15C to 30C (59F to 86F).

• This indication was approved under accelerated approval based on overall response rate and duration of response; continued approval may depend on verification and description of clinical benefit in confirmatory trials.

• Cardiovascular: QTc (at baseline and periodically during therapy); cardiac function, including left ventricular ejection fraction (at baseline and during therapy)
• Metabolic: Electrolytes (at baseline and periodically during therapy)
• Respiratory: For new/worsening pulmonary symptoms indicative of ILD/pneumonitis

• Read the US FDA-approved patient labeling (Patient Information).
• Inform health care provider of symptoms indicative of significant QTc prolongation (including dizziness, lightheadedness, syncope) and about the use of any heart medications.
• Contact health care provider immediately to report new/worsening respiratory symptoms (e.g., cough, shortness of breath, chest pain).
• Contact health care provider immediately if signs/symptoms of heart failure (e.g., palpitations, shortness of breath, chest pain, syncope) develop.
• Promptly start antidiarrheal treatment (e.g., loperamide), increase oral fluids and electrolyte intake, and contact health care provider if diarrhea occurs.
• Inform health care provider of a known/suspected pregnancy.
• Females of childbearing potential: Use effective nonhormonal contraception during therapy and for 1 month after the last dose.
• Male patients with female partners of childbearing potential: Use effective contraception during therapy and for 1 week after the last dose.
• Do not breastfeed during therapy and for 1 week after the last dose.
• Avoid grapefruit or grapefruit juice while taking this drug.
• If a dose is missed by 6 hours or if vomiting occurs, skip the dose and resume treatment as prescribed the next day.

Frequently asked questions

• How effective is Exkivity (mobocertinib) for NSCLC?