LUMAKRAS

What it is

LUMAKRAS contains sotorasib. Each film-coated tablet contains sotorasib 120 mg. Sotorasib is a KRAS G12C inhibitor, which covalently and irreversibly binds to the unique cysteine of KRAS G12C. Inactivation of KRAS G12C by sotorasib blocks tumour cell signalling and survival, inhibits cell growth, and promotes apoptosis selectively in tumours harbouring KRAS G12C, an oncogenic driver of tumorigenesis across multiple cancer types. This medicinal product is subject to additional monitoring in Australia. This will allow quick identification of new safety information.

Approved indications

— Treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) who have received at least one prior systemic therapy for advanced disease.

Dosing overview

The recommended dose of LUMAKRAS is 960 mg (as eight 120 mg tablets) orally once daily until disease progression or unacceptable toxicity. Take LUMAKRAS at the same time each day with or without food. Confirm the presence of a KRAS G12C mutation using a validated test prior to initiation of LUMAKRAS.

Key safety warnings

LUMAKRAS can cause hepatotoxicity and increased alanine aminotransferase (ALT) or increased aspartate aminotransferase (AST) which may lead to drug-induced liver injury and hepatitis. In the pooled safety population of patients with NSCLC who received single agent LUMAKRAS 960 mg, hepatotoxicity occurred in 27% of patients, of which 16% were Grade ≥ 3. Monitor liver function tests (ALT, AST, alkaline phosphatase and total bilirubin) prior to the start of LUMAKRAS, 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. Interstitial Lung Disease (ILD)/pneumonitis occurred in 2.2% of patients, of which 1.1% were Grade ≥ 3, and 1 case was fatal. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnoea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other causes of ILD/pneumonitis are identified.

Contraindications

LUMAKRAS is contraindicated in patients with hypersensitivity to sotorasib or any of the excipients. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Regulatory history

LUMAKRAS was first included in the Australian Register of Therapeutic Goods on 30 March 2022. The medicine has provisional approval in Australia for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy for advanced disease. The decision to approve this indication has been made on the basis of the objective response rate (ORR) and the duration of response (DOR). Continued approval of this indication depends on the verification and description of benefit in confirmatory trials.