• Sotorasib is indicated in the treatment of KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) in adults who have received at least one prior systemic therapy.
• 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.
• Sotorasib is indicated for the treatment of adults with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer, as determined by a Food and Drug Administration-approved test, who have received at least one prior systemic therapy
• Sotorasib is indicated in the treatment of KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) in adults who have received at least one prior systemic therapy.^[rx]
• Locally Advanced Non-Small Cell Lung Cancer
• Metastatic Non-Small Cell Lung Cancer

Use in Cancer

Sotorasib is approved to treat:

• Non-small cell lung cancer (NSCLC) has spread and has a KRAS p.G12C mutation. It is used in adults who have received at least one other systemic therapy.

Sotorasib is approved under FDA’s Accelerated Approval Program. As a condition of approval, confirmatory trial(s) must show that it provides a clinical benefit to these patients. Sotorasib is also being studied in the treatment of other types of cancer.

Contraindications

• a type of inflammation of the lung called interstitial pneumonitis
• abnormal liver function tests
• a patient who is producing milk and breastfeeding
• lung tissue problem

Dosage

Strengths: 120 mg

Non-Small Cell Lung Cancer

• 960 mg orally once a day
• Duration of therapy: Until disease progression or unacceptable toxicity
• This indication is approved under accelerated approval based on overall response rate and duration of response; continued approval may depend on verification and description of clinical benefit in confirmatory trial(s). For the treatment of patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least 1 prior systemic therapy

Dose Adjustments

If hepatotoxicity develops during therapy:

• Grade 2 AST or ALT with symptoms OR Grade 3 to 4 AST or ALT: This drug should be withheld until recovery to Grade 1 or less or baseline; therapy should resume at the next lower dose level.
• First dose reduction: 480 mg orally once a day
• Second dose reduction: 240 mg orally once a day
• AST or ALT greater than 3 times the upper limit of normal (3 x ULN) with total bilirubin greater than 2 x ULN without alternative causes: This drug should be permanently discontinued.
• If adverse reactions occur, a maximum of 2 dose reductions are permitted. This drug should be discontinued if patients are unable to tolerate the minimum dose of 240 mg orally once a day.

Dose Reduction for Adverse Reactions:

• First dose reduction: 480 mg orally once a day
• Second dose reduction: 240 mg orally once a day

Dose Modifications for Adverse Reactions:
Interstitial lung disease (ILD)/pneumonitis:

• Any Grade: This drug should be withheld if ILD/pneumonitis is suspected; this drug should be permanently discontinued if ILD/pneumonitis is confirmed.

Nausea or vomiting despite appropriate supportive care (including antiemetic therapy):

• Grade 3 to 4: This drug should be withheld until recovery to Grade 1 or less or baseline; therapy should resume at the next lower dose level.

Diarrhea despite appropriate supportive care (including antidiarrheal therapy):

• Grade 3 to 4: This drug should be withheld until recovery to Grade 1 or less or baseline; therapy should resume at the next lower dose level.

Other adverse reactions:

• Grade 3 to 4: This drug should be withheld until recovery to Grade 1 or less or baseline; therapy should resume at the next lower dose level.

Coadministration with Acid-Reducing Agents:

• Coadministration of proton pump inhibitors and H2-receptor antagonists with this drug should be avoided.
• If treatment with an acid-reducing agent cannot be avoided, this drug should be administered 4 hours before or 10 hours after administration of a local antacid.

Administration advice:

• Prior to use, select patients based on the presence of KRAS G12C mutation in tumor or plasma specimens; if no mutation is detected in a plasma specimen, test tumor tissue.
• For information on US FDA-approved tests for detection of KRAS G12C: http://www.fda.gov/CompanionDiagnostics
• Administer this drug at the same time each day with or without food.
• Swallow tablets whole; do not chew, crush, or split tablets.
• If patient has difficulty swallowing solids:
• Disperse tablets in 120 mL (4 ounces) of noncarbonated, room-temperature water without crushing; do not use other liquids.
• Stir until tablets are dispersed into small pieces (tablets will not completely dissolve) and drink immediately or within 2 hours; the mixture appearance 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 not consumed immediately, stir the mixture again to ensure that tablets are dispersed.
• If a dose is missed by more than 6 hours, administer the next dose as prescribed the next day; do not administer 2 doses at the same time to make up for the missed dose.
• If vomiting occurs after dosing, do not administer an additional dose; administer the next dose as prescribed the next day.

Patient advice:

• Read the US FDA-approved patient labeling (Patient Information).
• Contact health care provider immediately for signs/symptoms of liver dysfunction or to report new/worsening respiratory symptoms.
• Do not breastfeed during therapy and for 1 week after the last dose.
• Avoid proton pump inhibitors and H2-receptor antagonists while taking this drug; if coadministration cannot be avoided, take this drug 4 hours before or 10 hours after a locally-acting antacid.
• If a dose is missed by more than 6 hours, resume therapy as prescribed the next day.

Side Effects

The Most Common

• diarrhea
• vomiting
• nausea
• constipation
• loss of appetite
• stomach pain
• tiredness
• muscle or bone pain
• joint pain
• rash
• yellowing of skin or eyes, dark-colored urine, bleeding or bruising more easily than normal, loss of appetite, decreased energy, or pain on right side of stomach area
• shortness of breath, cough, or fever.

More common

• Chest pain or tightness
• cough
• dark urine
• fever or chills
• light-colored stools
• loss of appetite
• nausea or vomiting
• sneezing
• sore throat
• stomach pain
• trouble breathing
• unusual tiredness or weakness
• yellow eyes or skin

Rare

• Blistering, crusting, irritation, itching, or reddening of the skin
• constipation
• cracked, dry, scaly skin
• diarrhea
• difficulty in moving
• joint or bone pain
• lack or loss of strength
• muscle aches, cramps, pain, or stiffness
• rash with flat lesions or small raised lesions on the skin
• swelling of the hands, ankles, feet, or lower legs
• swelling of the testes

Drug Interactions

Pregnancy

There are no available data on LUMAKRAS use in pregnant women. In rat and rabbit embryo-fetal development studies, oral sotorasib did not cause adverse developmental effects or embryo-lethality at exposures up to 4.6 times the human exposure at the 960 mg clinical dose
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically
recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Lactation

There are no data on the presence of sotorasib or its metabolites in human milk, the effects on the breastfed child, or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to