Source: European Medicines Agency (EU) Revision Year: 2022 Publisher: Amgen Europe B.V., Minervum 7061, 4817 ZK Breda, The Netherlands
LUMYKRAS as monotherapy is indicated for the treatment of adults with advanced non-small cell lung cancer (NSCLC) with KRAS G12C mutation and who have progressed after at least one prior line of systemic therapy.
Treatment with LUMYKRAS must be initiated by a physician experienced in the use of anticancer medicinal products.
The presence of a KRAS G12C mutation must be confirmed using a validated test prior to initiation of LUMYKRAS therapy.
The recommended dose is 960 mg sotorasib (eight 120 mg tablets) once daily, at the same time each day.
Treatment with LUMYKRAS is recommended until disease progression or unacceptable toxicity.
If less than 6 hours have passed since the scheduled time of dosing, the patient should take the dose as normal. If more than 6 hours have passed since the scheduled time of dosing, the patient must not take the dose. Treatment should be continued as prescribed the next day.
If vomiting occurs after taking LUMYKRAS, the patient must not take an additional dose on the same day, and treatment must be continued as prescribed the next day.
Dosing should be modified based on LUMYKRAS toxicity. The dose reduction rules outlined in section 4.2 are based on clinical data. Pharmacokinetic data do suggest a similar exposure at lower sotorasib doses. Dose reduction levels are summarised in table 1. Dose modifications for adverse reactions are provided in table 2 (see section 5.2).
If toxicity events occur, a maximum of two dose reductions are permitted. LUMYKRAS must be discontinued if patients are unable to tolerate the minimum dose of 240 mg once daily.
Table 1. Recommended sotorasib dose reduction levels:
| Dose reduction level | Dose |
|---|---|
| Starting dose | 960 mg (eight 120 mg tablets) once daily |
| First dose reduction | 480 mg (four 120 mg tablets) once daily |
| Second dose reduction | 240 mg (two 120 mg tablets) once daily |
Table 2. Recommended dose modifications for sotorasib:
| Adverse reaction | Severitya | Dose modification |
|---|---|---|
| Hepatotoxicity | Grade 2 AST or ALT with symptoms or Grade ≥ 3 AST or ALT | • Stop treatment until recovered to ≤ grade 1 or to baseline grade • After recovery, resume treatment at the next dose reduction level |
| AST or ALT > 3 × ULN with total bilirubin > 2 × ULN, in the absence of alternative causes | • Permanently discontinue treatment | |
| Interstitial Lung Disease (ILD)/pneumonitis | Any grade | • Stop treatment if ILD/pneumonitis is suspected. • Permanently discontinue treatment if ILD/pneumonitis is confirmed. |
| Nausea, vomiting, or diarrhoea persisting despite supportive care (including anti-emetic or anti-diarrhoeal therapy) | Grade ≥ 3 | • Stop treatment until recovered to ≤ grade 1 or to baseline grade • After recovery, resume treatment at the next dose reduction level |
| Other medicinal product- related toxicity | Grade ≥ 3 | • Stop treatment until recovered to ≤ grade 1 or to baseline grade • After recovery, resume treatment at the next dose reduction level |
ALT = alanine aminotransferase; AST = aspartate aminotransferase; ULN = upper limit of normal
a Grading defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
Co-administration of proton pump inhibitors (PPIs) or H2 receptor antagonists with LUMYKRAS is not recommended. If treatment with an acid-reducing agent is required a local antacid may be used, LUMYKRAS should be taken either 4 hours before or 10 hours after administration of a local antacid (see section 4.5).
The limited data on the safety and efficacy of LUMYKRAS in patients aged 75 years and older do not suggest that a dose adjustment is required in elderly patients (see section 4.8 and 5.2).
No dose adjustment is recommended for patients with mild hepatic impairment (AST or ALT <2.5 × ULN or total bilirubin <1.5 × ULN). Administration of sotorasib in subjects with moderate and severe hepatic impairment is not recommended.
No dose adjustment is recommended for patients with mild renal impairment (creatine clearance, CrCL, ≥60 mL/min). LUMYKRAS has not been studied in patients with moderate or severe renal impairment (CrCL <60 mL/min). Therefore, caution should be exercised when treating patients with moderate, severe and end stage renal impairment (see section 5.2).
There is no relevant use of LUMYKRAS in the paediatric population in the treatment of non-small cell lung cancer.
LUMYKRAS is for oral use. The tablets must be swallowed whole. There are no data to support the administration of LUMYKRAS if the tablets are chewed, crushed, or split but the tablets can be dispersed in water (see below). The tablets can be taken with or without food.
Patients should disperse tablets in 120 mL of non-carbonated, room-temperature water, without crushing them. Other liquids must not be used. Patients should stir until tablets are dispersed into small pieces (the tablet will not dissolve completely) and drink immediately. The appearance of the mixture may range from pale to bright yellow. The container must be rinsed with an additional 120 mL of water, which should be drunk immediately. If it is not drunk immediately, patients must stir again to ensure that the tablets are dispersed. The dispersion must be discarded if it is not drunk within 2 hours.
If administration through a nasogastric (NG) tube or percutaneous endoscopic gastrostomy (PEG) tube is required, follow the process above for the initial dispersion and for the residual rinse of the 120 mg tablets. The dispersed suspension and rinse should be administered as per the NG or PEG tube manufacturer’s instructions with appropriate water flushes. Administer the dispersion within 2 hours of preparation, stored at room temperature.
In the event of an overdose, the patient should be treated symptomatically, and supportive measures instituted as required. There is no specific antidote for overdose with LUMYKRAS.
This medicinal product does not require any special storage conditions.
PVC/PE/PVDC blisters with aluminium foil backing containing 8 film-coated tablets. Pack sizes of 240 film-coated tablets (1 carton with 30 blisters) and multipack with 720 (3 × 240) film-coated tablets.
HDPE bottle with a child-resistant polypropylene cap and aluminium foil induction seal liner containing 120 film-coated tablets. Pack size of 240 film-coated tablets (1 carton with 2 bottles).
Not all pack sizes may be marketed.
This medicinal product may pose a risk to the environment (see section 5.3). Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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