LUMYKRAS

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.

Posology The recommended dose of LUMYKRAS is 960 mg (eight 120 mg tablets) orally once daily, at the same time each day, with or without food. Duration of treatment Treatment with LUMYKRAS is recommended until disease progression or unacceptable toxicity.

Missed doses 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.

Additional doses should not be taken in place of a missed dose. 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. Dose modifications Dosing should be modified based on LUMYKRAS toxicity.

Dose reduction levels are summarised in table 1. Dose modifications for adverse reactions are provided in table 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 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 Hepatotoxicity AST or ALT > 3 × ULN with total bilirubin > 2 × ULN, in the absence of alternative causes • Permanently discontinue treatment Interstitial Lung Any Grade • Stop treatment if Adverse reaction Severitya Dose modification Disease/(ILD)/pneumonitis ILD/pneumonitis is suspected • Permanently discontinue if ILD/pneumonitis is confirmed Nausea or vomiting despite appropriate supportive care (including anti-emetic therapy) Grade 3 to 4 • Stop treatment until recovered to ≤ grade 1 or to baseline grade • After recovery, resume treatment at the next dose reduction level Diarrhoea despite appropriate supportive care (including anti-diarrhoeal therapy) Grade 3 to 4 • Stop treatment until recovered to ≤ grade 1 or to baseline grade • After recovery, resume treatment at the next dose reduction level Other adverse reactions Grade 3 to 4 • Stop treatment until recovered to ≤ grade 1 or to baseline grade • After recovery, resume treatment at the next dose reduction level Special populations Elderly In clinical studies, no overall differences in safety or efficacy were observed between elderly patients (≥ 65 years old) and younger patients.

2). 2). Dose adjustment should be considered in patients with severe hepatic impairment (Child-Pugh C). There are no data on the clinical safety and efficacy of multiple doses of LUMYKRAS when administered to patients with severe hepatic impairment (Child-Pugh C).

LUMYKRAS should be used with caution in patients with severe hepatic impairment. Renal impairment Based on population pharmacokinetic analysis, no dose adjustment is recommended for patients with mild renal impairment (creatine clearance, CrCL ≥ 60 mL/min).

2). Paediatric population The safety and efficacy of LUMYKRAS in children and adolescents aged less than 18 years have not been established. No data are available. 0 Method of administration LUMYKRAS is for oral use. The tablets should normally be swallowed whole, unless the patient has difficulty swallowing solids, in which case the following instruction should be followed.

Administration to patients who have difficulty swallowing solids Patients should disperse tablets in 120 mL of non-carbonated, room-temperature water without crushing. Other liquids must not be used. Patients should stir until the tablets are dispersed into small pieces (the tablet will not completely dissolve) and drink it 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.

Summary of the safety profile The safety of LUMYKRAS was evaluated in 359 patients with KRAS G12C-mutated solid tumours who received 960 mg orally once daily as monotherapy. 02 to 21). The most common adverse reactions were diarrhoea (34%), musculoskeletal pain (31%), nausea (25%), fatigue (21%), hepatotoxicity (19%) and cough (16%).

The most common severe (grade ≥ 3) adverse reactions were increased ALT (5%), increased AST (4%), and diarrhoea (4%). The most common adverse reactions leading to permanent discontinuation of treatment were increased ALT (1%), increased AST (1%) and drug-induced liver injury (1%).

The most common adverse reactions leading to dose modification were increased ALT (6%), increased AST (6%), and diarrhoea (6%). The most common laboratory abnormalities (≥ 25%) were decreased lymphocytes, decreased haemoglobin, increased AST, decreased calcium, increased urine protein, increased ALT, increased alkaline phosphatase, and decreased sodium.

Tabulated list of adverse reactions Adverse reactions reported in LUMYKRAS clinical studies are displayed in table 3 below. Frequency is provided by MedDRA category: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 and < 1/1,000), very rare (< 10,000).

Within each system organ class, adverse reactions are presented in order of decreasing seriousness. Table 3. Adverse reactions MedDRA system organ class Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) MedDRA system organ class Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Blood and lymphatic system disorders Anaemia Nervous system disorders Headache Respiratory, thoracic and mediastinal disorders Dyspnoea Cougha Cardiovascular disorders Hypertension Gastrointestinal disorders Diarrhoea Nausea Vomiting Abdominal painb Constipation Hepatobiliary Disorders Hepatotoxicityc Musculoskeletal and connective tissue disorders Musculoskeletal paind General disorders and administration site conditions Fatigue Pyrexia Peripheral oedema Metabolism and nutrition disorders Decreased appetite Hypokalaemia Hyponatraemia Hypocalcaemia Infections Pneumonia Urinary tract infection Skin and subcutaneous tissue disorders Rash Investigations Blood alkaline phosphatase increased a Cough includes cough, productive cough, and upper-airway cough syndrome.

b Abdominal pain includes abdominal pain, abdominal pain upper, abdominal pain lower c Hepatotoxicity includes alanine aminotransferase increased, aspartate aminotransferase increased, blood bilirubin increased, drug-induced liver injury, hepatitis, hepatotoxicity, liver function test increased, and transaminases increased.

6% were Grade 4. 3 to 42). Increased ALT/AST leading to dose interruption or reduction occurred in 7% of patients. 7% of patients. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity.

8% of patients, all cases were Grade 3 or 4 at onset. The median time to first onset for ILD/pneumonitis was 2 weeks (range: 2 to 18 weeks). 6% of patients. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

Hepatotoxicity LUMYKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis. 8). These elevations improved or resolved with dose modification or permanent discontinuation of treatment and did not result in any cases of liver failure or fatal cases in clinical studies.

Cases of liver enzyme increase can be asymptomatic. Liver function tests (ALT, AST, and total bilirubin) must be monitored prior to the start of LUMYKRAS, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations.

2). 8). , dyspnoea, cough, fever). 2) Lactose intolerance Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. Sodium This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

1.