Usual Adult Dose for Non-Small Cell Lung Cancer

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

Use: For the treatment of patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations

Renal Dose Adjustments

Mild or moderate renal dysfunction (CrCl 30 to 89 mL/min): No adjustment recommended.
Severe renal dysfunction (CrCl less than 30 mL/min): Data not available

Comments:

• Recommended dosage has not been established for patients with severe renal dysfunction.

Liver Dose Adjustments

Mild or moderate liver dysfunction (Child-Pugh A or B): No adjustment recommended.
Severe liver dysfunction (Child-Pugh C): Data not available

During Therapy:
Increased ALT and/or AST without increased total bilirubin:

• Grade 3: This drug should be withheld until recovery to baseline ALT/AST; if recovered to baseline within 7 days, then this drug can be resumed at the same dose, otherwise it should be resumed at a reduced dose (225 mg orally once a day).
• Grade 4: This drug should be permanently discontinued.

• ALT and/or AST greater than 3 times the upper limit of normal (3 x ULN) with total bilirubin greater than 2 x ULN: This drug should be permanently discontinued.

• Grade 3: This drug should be withheld until recovery to baseline bilirubin; if recovered to baseline within 7 days, then this drug can be resumed at a reduced dose (225 mg orally once a day), otherwise it should be permanently discontinued.
• Grade 4: This drug should be permanently discontinued.

• Pharmacokinetics and safety have not been studied in severe liver dysfunction.

Dose Adjustments

Recommended dose reduction for adverse reaction management: 225 mg orally once a day
If patients are unable to tolerate 225 mg/day: This drug should be permanently discontinued.

Interstitial Lung Disease (ILD)/Pneumonitis:

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

• Grade 2: Dose level should be maintained; if intolerable, withholding this drug until resolved should be considered, then it should be resumed at a reduced dose.
• Grade 3: This drug should be withheld until resolved, then it should be resumed at a reduced dose.
• Grade 4: This drug should be permanently discontinued.

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Select patients for treatment based on the presence of MET exon 14 skipping alterations in plasma or tumor specimens.
• Testing for the presence of MET exon 14 skipping alterations in plasma specimens is recommended only if a tumor biopsy cannot be obtained.
• Reevaluate the feasibility of biopsy for tumor tissue testing if an alteration is not detected in a plasma specimen.
• A US FDA-approved test for detection of MET exon 14 skipping alterations in NSCLC for selecting patients for treatment with this drug is not available.
• Administer with food at about the same time each day.
• Swallow tablets whole; do not chew, crush or split tablets.

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

• 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.

• Hepatic: Liver function tests, including ALT, AST, and total bilirubin (before starting therapy, every 2 weeks during the first 3 months of therapy, then once a month or as clinically indicated)
• Respiratory: For new/worsening pulmonary symptoms indicative of ILD/pneumonitis

• Read the US FDA-approved patient labeling (Patient Information).
• Contact health care provider immediately to report new/worsening respiratory symptoms.
• Contact health care provider immediately for signs/symptoms of liver dysfunction.
• Females of childbearing potential and 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.
• If you missed a dose, take the dose as soon as possible; if your next dose is due within 8 hours, skip the missed dose and resume with the next scheduled dose.
• If vomiting occurs after a dose, take the next dose at the next scheduled time.