TEPMETKO

Treatment must be initiated and supervised by a physician experienced in the use of anticancer therapies. Assessment of METex14 skipping alterations status Prior to initiation of treatment with TEPMETKO the presence of METex14 skipping alterations should be confirmed by a validated test method using nucleic acids isolated from either tumour or plasma specimens.

Testing for the presence of METex14 skipping alterations in tissue specimens is recommended because of higher sensitivity. However, plasma specimens may be used in patients for whom a tumour biopsy cannot be obtained. If an alteration is not detected in a plasma specimen, the feasibility of biopsy for tumour tissue testing should be evaluated.

Posology The recommended dose is 450 mg tepotinib (2 tablets) taken once daily. Treatment should continue until disease progression or unacceptable toxicity. If a daily dose is missed, it can be taken as soon as remembered on the same day, unless the next dose is due within 8 hours.

Dose modification for adverse reactions Dose interruption, dose reduction or discontinuation of treatment with TEPMETKO may be required based on adverse reactions. The recommended dose reduction level for the management of adverse reactions is 225 mg (1 tablet) daily.

TEPMETKO should be permanently discontinued if patients are unable to tolerate 225 mg (1 tablet) daily. Detailed recommendations for dose modification are provided in the table below. 4) Any grade Withhold tepotinib if ILD is suspected.

Permanently discontinue tepotinib if ILD is confirmed. Grade 3 Withhold tepotinib until recovery to baseline ALT/AST. If recovered to baseline within 7 days, then resume tepotinib at the same dose; otherwise resume tepotinib at a reduced dose.

4) Grade 4 Permanently discontinue tepotinib. 4) ALT and/or AST greater than 3 times ULN with total bilirubin greater than 2 times ULN Permanently discontinue tepotinib. Recommended dose modifications for TEPMETKO for adverse reactions Adverse reaction Severity Dose modification Grade 3 Withhold tepotinib until recovery to baseline bilirubin.

If recovered to baseline within 7 days, then resume tepotinib at a reduced dose; otherwise permanently discontinue. 4) Grade 4 Permanently discontinue tepotinib. Grade 2 Maintain dose level. If intolerable, consider withholding tepotinib until resolved, then resume tepotinib at a reduced dose.

Summary of the safety profile The safety data described reflect exposure to tepotinib 450 mg once daily in 313 patients with advanced NSCLC harbouring METex14 skipping alterations included in the main clinical study (VISION). 4 weeks (range: 0 to 312 weeks).

8%). 0%). 9%. 0%). 7%. 2%). 1%. 6%). List of adverse reactions An asterisk (*) indicates that additional information on the respective adverse reaction is provided below the table. 0) * Additional information on the respective adverse reaction is provided below Adverse reactions in patients with NSCLC harbouring METex14 skipping alterations who received TEPMETKO in VISION System organ class/Adverse reaction TEPMETKO N=313 (cut-off date: Nov 2022) Frequency category All grades n (%) Grade ≥ 3 n (%) † ILD as per Integrated Assessment.

Includes terms interstitial lung disease, pneumonitis, and acute respiratory failure. 3%). 1 weeks). 0%). 3%) of acute respiratory failure secondary to ILD was reported. 4. 9%) patients, respectively. 6%) of patients, respectively. 1 weeks) for any grade of ALT and/or AST increase.

6%) required a dose reduction of tepotinib. 57 weeks […]

g. 8). g. dyspnoea, cough, fever). TEPMETKO should be withheld immediately and patients should be promptly investigated for alternative diagnosis or specific aetiology of interstitial lung disease. TEPMETKO must be permanently discontinued if interstitial lung disease is confirmed and the patient be treated according to local clinical practice.

8). Liver enzymes (ALT and AST) and bilirubin should be monitored prior to the start of TEPMETKO, every 2 weeks during the first 3 months of treatment, then once a month. 2). 6). Women of childbearing potential or male patients with female partners of childbearing potential should be advised of the potential risk to a foetus.

Women of childbearing potential should use effective contraception during TEPMETKO treatment and for at least 1 week after the last dose. Male patients with female partners of childbearing potential should use barrier contraception during TEPMETKO treatment and for at least 1 week after the last dose.

2). 8) may be the result of inhibition of active tubular secretion rather than renal injury. Renal function estimates that rely on serum creatinine (creatinine clearance or estimated glomerular filtration rate) should be interpreted with caution considering this effect.

In case of blood creatinine increase while on treatment, it is recommended that further assessment of the renal function be performed to exclude renal impairment. Lactose content TEPMETKO contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

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