Tepotinib is an oral MET tyrosine kinase inhibitor indicated for the treatment of non-small cell lung cancer harboring MET exon 14 skipping mutations.

I. Indications and Patient Selection

1. Applicable Cancer Type

(1) Tepotinib is indicated for adult patients with metastatic non-small cell lung cancer (NSCLC).

(2) Its target is the mesenchymal-epithelial transition factor (MET) exon 14 skipping mutation, which leads to sustained activation of the MET pathway, promoting tumor growth and metastasis.

2. Genetic Testing Requirements

(1) Prior to treatment, the presence of MET exon 14 skipping mutation in the tumor must be confirmed by genetic testing.

(2) Testing specimens may be tumor tissue biopsy samples or plasma circulating tumor DNA.

(3) Tissue biopsy is preferentially recommended; plasma testing should only be considered when tissue samples are not available.

(4) If plasma testing yields a negative result, the feasibility of tissue biopsy re-evaluation should still be assessed.

3. Unsuitable Populations

(1) The safety and efficacy of this drug in pediatric patients have not been established; it is not recommended for individuals under 18 years of age.

(2) Additionally, patients with severe hepatic or renal impairment lacking adequate usage data should be carefully evaluated.

II. Standard Dosage and Administration

1. Recommended Dose and Timing

(1) The standard dose is 450 mg (i.e., two 225-mg tablets) once daily, taken orally with food.

(2) The dose should be taken at approximately the same time each day to maintain stable plasma concentrations.

(3) Treatment should continue until unequivocal disease progression or unacceptable toxicity occurs.

2. Correct Administration Method

(1) Tablets must be swallowed whole; do not chew, crush, or split.

(2) For patients with difficulty swallowing, the tablet may be placed in approximately 30 mL of non-carbonated drinking water and gently stirred to disperse into small fragments (it will not completely dissolve). The suspension must be consumed within 1 hour, followed by rinsing the cup with an equal volume of water and drinking it to ensure the full dose is delivered.

3. Missed Dose and Vomiting Management

(1) If a dose is missed, it may be taken as soon as remembered on the same day; however, if it is less than 8 hours until the next scheduled dose, the missed dose should be skipped and the next dose taken on time.

(2) If vomiting occurs after taking the dose, do not take an additional dose; proceed with the next scheduled dose as planned.

III. Dose Adjustment Principles

1. First Dose Reduction Criteria

(1) When adverse reactions requiring intervention occur, the recommended first dose reduction is to 225 mg (i.e., one tablet) daily.

(2) If the patient cannot tolerate the reduced dose, the drug must be permanently discontinued.

2. Dosage Instructions for Special Populations

(1) No dose adjustment is required for patients with mild to moderate hepatic impairment (Child-Pugh A or B), but enhanced monitoring is recommended.

(2) No data are available for severe hepatic impairment; use is not recommended.

(3) No dose adjustment is required for patients with mild to moderate renal impairment (creatinine clearance 30–89 mL/min); no recommended dose is available for severe renal impairment due to lack of study data.

3. Considerations for Concomitant Medications

(1) Tepotinib may increase the plasma concentrations of certain P-glycoprotein substrate drugs.

(2) If co‑administered with such sensitive substrates (e.g., certain anticoagulants), it should be evaluated whether dose adjustment of those substrates is needed; refer to the respective prescribing information for specific guidance.