Lumykras

Treatment with LUMYKRAS must be initiated by a physician experienced in the use of anticancer medicinal products. 3 The presence of a KRAS G12C-mutation must be confirmed using a validated test prior to initiation of LUMYKRAS therapy.

Posology The recommended dose is 960 mg sotorasib (eight 120 mg tablets or four 240 mg tablets) once daily, at the same time each day. Duration of treatment Treatment with LUMYKRAS is recommended until disease progression or unacceptable toxicity.

Missed doses or vomiting 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. Dose modifications Dosing should be modified based on LUMYKRAS toxicity.

2 are based on clinical data. 2). Dose reduction levels are summarised in table 1. Dose modifications for adverse reactions are provided in table 2. A maximum of two dose reductions are recommended for management of an adverse reaction (see table 1).

Discontinue LUMYKRAS if an adverse reaction cannot be managed after two dose reductions and 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 or four 240 mg tablets) once daily First dose reduction 480 mg (four 120 mg tablets or two 240 mg tablets) once daily Second dose reduction 240 mg (two 120 mg tablets or one 240 mg tablet) once daily 4 Table 2.

Recommended dose modifications for sotorasib Adverse reaction Severitya Dose modification Hepatotoxicity AST or ALT > 3 × and up to 5 × ULN (or > 3 × and up to 5 × baseline if baseline abnormal) with symptoms or AST or ALT > 5 × ULN (or > 5 × baseline if baseline abnormal), in the absence of alternative causes.

• Withhold treatment • Closely monitor liver function until recovered to ≤ 3 × ULN or to ≤ 3 × baseline if baseline abnormal. 5 × ULN (for subjects not on anticoagulation therapy), in the absence of alternative causes. • Permanently discontinue treatment if no alternative cause is identified.

Summary of the safety profile Adverse drug reactions (ADRs) described in table 3 reflect exposure to sotorasib 960 mg once daily as monotherapy in 740 patients with KRAS G12C-mutated solid tumours across multiple clinical studies, including CodeBreaK 200, CodeBreaK 100 phase 2 part A, and CodeBreaK 100 phase 2 part B (dose comparison sub-study) and three phase 1 studies.

1%). 6%). 1%) and DILI (1%). 4%) and vomiting (2%). 9 Tabulated list of adverse reactions Adverse reactions reported in LUMYKRAS clinical studies are displayed in table 3 below. Frequency categories are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000), and not known (cannot be estimated from available data).

Within each system organ class, adverse reactions are presented in order of decreasing seriousness. The safety of LUMYKRAS was evaluated in 740 patients with KRAS G12C-mutated solid tumours who received 960 mg orally once daily as monotherapy.

2 months (range: 0 to 41). Table 3. 4). 1% of patients, with a median time to onset of 6 weeks (range: 1 to 103) and 6 weeks (range: 0 to 42), respectively. 7% of patients. 9% of patients. 8% of patients. A case of fatal ILD occurred in a patient with metastatic NSCLC stage IVB treated with LUMYKRAS in a clinical trial.

The patient developed lower respiratory tract infection with a fatal outcome despite steroids and antibiotics treatment. The fatal ILD occurred in a setting of massive disease progression. 3 weeks). 4). 2). 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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Hepatotoxicity Sotorasib can cause hepatotoxicity, which may lead to drug-induced liver injury (DILI) and hepatitis. Sotorasib has been associated with transient elevations of serum transaminases (ALT and AST), alkaline phosphatase and total bilirubin in 960 mg monotherapy clinical trials.

In a total of 740 patients with KRAS G12C-mutated solid tumours who received LUMYKRAS 960 mg monotherapy daily, the incidence for hepatotoxicity is highest in the sub-group of patients with recent (≤ 3 months) immunotherapy (38%) prior to starting LUMYKRAS, as compared to those who started LUMYKRAS either more than 3 months after last dose of immunotherapy (17%) or those who never received immunotherapy (22%).

Regardless of time from prior immunotherapy, 87% of elevations improved or resolved with interruption of LUMYKRAS treatment and treatment with corticosteroids. Elevated liver enzymes led to discontinuation of treatment in 10%, 2% and 0% of patients with prior immunotherapy within ≤ 3 months, with prior immunotherapy within > 3 months and no prior immunotherapy, respectively.

Among 740 patients with KRAS G12C-mutated solid tumours who received 960 mg orally once daily, 26% experienced hepatotoxicity and 13% had hepatotoxicity leading to dose interruption and/or dose reduction. Overall, 41% of patients with hepatotoxicity 6 received concurrent corticosteroids.

Cases of liver enzyme increase can be asymptomatic. Patients should be monitored for liver function (ALT, AST, alkaline phosphatase and total bilirubin) 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 with recent immunotherapy and in patients with serious hepatotoxicity events.

2). Interstitial Lung Disease (ILD)/pneumonitis LUMYKRAS can cause ILD/pneumonitis that can be fatal. 8). Recent (≤ 3 months) immunotherapy prior to starting LUMYKRAS may be considered a risk factor for ILD/pneumonitis. g. dyspnoea, cough, fever).

1.