LUMAKRAS

LUMAKRAS- sotorasib tablet, coated
Amgen Inc

1 INDICATIONS AND USAGE

LUMAKRAS is indicated for the treatment of adult patients with KRAS G12C -mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test [see Dosage and Administration (2.1)], who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR) [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

2 DOSAGE AND ADMINISTRATION

2.1 Patient Selection

Select patients for treatment of locally advanced or metastatic NSCLC with LUMAKRAS based on the presence of KRAS G12C mutation in tumor or plasma specimens [see Clinical Studies (14)]. If no mutation is detected in a plasma specimen, test tumor tissue.

Information on FDA-approved tests for the detection of KRAS G12C mutations is available at: http://www.fda.gov/CompanionDiagnostics.

2.2 Recommended Dosage and Administration

The recommended dosage of LUMAKRAS is 960 mg (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 [see Clinical Pharmacology (12.3)]. Swallow tablets whole. Do not chew, crush or split tablets. If a dose of LUMAKRAS is missed by more than 6 hours, take the next dose as prescribed the next day. Do not take 2 doses at the same time to make up for the missed dose.

If vomiting occurs after taking LUMAKRAS, do not take an additional dose. Take the next dose as prescribed the next day.

Administration to Patients Who Have Difficulty Swallowing Solids

Disperse tablets in 120 mL (4 ounces) of non-carbonated, room-temperature water without crushing. No other liquids should be used. Stir until tablets are dispersed into small pieces (the tablets will not completely dissolve) and drink immediately or within 2 hours. The appearance of the mixture may range from pale yellow to bright yellow. Swallow the tablet dispersion. Do not chew pieces of the tablet. Rinse the container with an additional 120 mL (4 ounces) of water and drink. If the mixture is not consumed immediately, stir the mixture again to ensure that tablets are dispersed.

2.3 Dosage Modifications for Adverse Reactions

LUMAKRAS dose reduction levels are summarized in Table 1. Dosage modifications for adverse reactions are provided in Table 2.

If adverse reactions occur, a maximum of two dose reductions are permitted. Discontinue LUMAKRAS if patients are unable to tolerate the minimum dose of 240 mg once daily.

Table 1. Recommended LUMAKRAS Dose Reduction Levels for Adverse Reactions
Dose Reduction Level Dose
First dose reduction 480 mg (4 tablets) once daily
Second dose reduction 240 mg (2 tablets) once daily
Table 2. Recommended LUMAKRAS Dosage Modifications for Adverse Reactions
Adverse Reaction Severity * Dosage Modification
ALT = alanine aminotransferase; AST = aspartate aminotransferase; ULN = upper limit of normal
*
Grading defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
Hepatotoxicity [see Warnings and Precautions (5.1)] Grade 2 AST or ALT with symptomsorGrade 3 to 4 AST or ALT
  • Withhold LUMAKRAS until recovery to ≤ Grade 1 or baseline.
  • Resume LUMAKRAS at the next lower dose level.
AST or ALT > 3 × ULN with total bilirubin > 2 × ULN in the absence of alternative causes
  • Permanently discontinue LUMAKRAS.
Interstitial Lung Disease (ILD)/ pneumonitis [see Warnings and Precautions (5.2)] Any Grade
  • Withhold LUMAKRAS if ILD/pneumonitis is suspected.
  • Permanently discontinue LUMAKRAS if ILD/pneumonitis is confirmed.
Nausea or vomiting despite appropriate supportive care (including anti-emetic therapy)[see Adverse Reactions (6.1)] Grade 3 to 4
  • Withhold LUMAKRAS until recovery to ≤ Grade 1 or baseline.
  • Resume LUMAKRAS at the next lower dose level.
Diarrhea despite appropriate supportive care (including anti-diarrheal therapy) [see Adverse Reactions (6.1)] Grade 3 to 4
  • Withhold LUMAKRAS until recovery to ≤ Grade 1 or baseline.
  • Resume LUMAKRAS at the next lower dose level.
Other adverse reactions[see Adverse Reactions (6.1)] Grade 3 to 4
  • Withhold LUMAKRAS until recovery to ≤ Grade 1 or baseline.
  • Resume LUMAKRAS at the next lower dose level.

2.4 Coadministration of LUMAKRAS with Acid-Reducing Agents

Avoid coadministration of proton pump inhibitors (PPIs) and H2 receptor antagonists with LUMAKRAS. If treatment with an acid-reducing agent cannot be avoided, take LUMAKRAS 4 hours before or 10 hours after administration of a local antacid [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

3 DOSAGE FORMS AND STRENGTHS

Tablets: 120 mg, yellow, oblong-shaped, immediate release, film-coated, debossed with “AMG” on one side and “120” on the opposite side.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Hepatotoxicity

LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis. Among 357 patients who received LUMAKRAS in CodeBreaK 100 [see Adverse Reactions (6.1)] , hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. The median time to first onset of increased ALT/AST was 9 weeks (range: 0.3 to 42). Increased ALT/AST leading to dose interruption or reduction occurred in 7% of patients. LUMAKRAS was discontinued due to increased ALT/AST in 2.0% of patients. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity.

Monitor liver function tests (ALT, AST, 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. Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction [see Dosage and Administration (2.3) and Adverse Reactions (6.1)].

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