Instructions for use of Sotoracib (AMG510)

1. Common names:Sotorasib, AMG510

Product name: USLUMAKRAS, EU LUMYKRAS

Other names: Sotolasib, Sotolasib, Sotolasib

2. Indications:

Sotorasib (AMG510, Sotorasib) is indicated for the 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, as determined by an FDA-approved test.

3. Usage and dosage:

1. Before treatment: Based on the presence of KRAS G12C mutations in tumors or plasma samples, sotoraxib is selected to treat patients with locally advanced or metastatic NSCLC. If no mutations are detected in the plasma sample, the tumor tissue is tested.

2. Recommended dose: The recommended dose of sotorasiib is 960 mg (3 320 mg tablets or 4 240 mg tablets or 8 120 mg tablets) orally once daily until disease progression or unacceptable toxicity occurs. Take it at the same time every day, with or without food.

3. Medication management: Sotoraxibu tablets can be swallowed whole. Do not chew, crush, or split tablets. If a dose 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 a missed dose. If vomiting occurs after taking this dose, do not take additional doses. Take your next dose as prescribed the next day.

(1) Medication for patients with difficulty swallowing solids

Disperse sotorasiib tablets in120 mL (4 ounces) of non-carbonated room temperature water without crushing. No other liquids should be used. Stir or swirl the cup for about 3 minutes until the tablets are dispersed into small pieces (the tablets will not completely dissolve), then drink immediately or within 2 hours. The mixture can range from pale to bright yellow in appearance. Swallow the tablet dispersion. Do not chew tablet fragments. Rinse container with another 120mL (4 ounces) of water and drink. If the mixture is not consumed immediately, stir the mixture again to ensure tablet dispersion.

4. Dose adjustment: Patients may experience adverse reactions when using sotoraxib. Doctors may adjust the drug dose according to the severity of the condition, and are allowed to reduce the dose by up to two times. The first dose will be reduced to 480 mg each time (four 120 mg tablets); the second dose will be reduced to 240 mg each time (two 120 mg tablets); if the patient cannot tolerate the minimum dose of 240 mg once daily, discontinue sotorasib.

(1) Drug interactions: Avoid coadministration of proton pump inhibitors (PPIs) and H2 receptor antagonists with sotoraxib. If this is unavoidable, take sotorasiib 4 hours before or 10 hours after the topical antacid.

4. Adverse reactions:

In clinical studies of sotoraxib, the most common adverse reactions (≥20%) were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough. The most common laboratory abnormalities (≥25%) were lymphopenia, decreased hemoglobin, increased aspartate aminotransferase, increased alanine aminotransferase, decreased calcium, increased alkaline phosphatase, increased urinary protein, and decreased sodium.

5. Supply and storage:

Sotoraxib is availableas 120 mg, 240 mg, and 320 mg tablets and can be stored at 20°C to 25°C (68°F to 77°F). Allows adjustment over temperature range of 15°C to 30°C (59°F to 86°F).

6. Taboo:

None.

7. Mechanism of action:

Sotoracib is an inhibitor of KRAS G12C, a tumor-restricted, mutated, oncogenic form of the RAS GTPase (KRAS). Sotorasiib forms an irreversible covalent bond with the unique cysteine u200bu200bof KRASG12C, locking the protein in an inactive state and preventing downstream signaling without affecting wild-type KRAS. Sotorasiib blocks KRAS signaling, inhibits cell growth and promotes apoptosis only in the KRAS G12C tumor cell line.

Sotorasiib inhibits KRASG12C in vitro and in vivoKRASG12C with minimal detectable off-target activity. In a mouse tumor xenograft model, sotorasiib treatment resulted in tumor regression and prolonged survival and was associated with anti-tumor immunity in the KRAS G12C model.

8. Special groups:

1. Women: There are no data on the presence of sotorasibu or its metabolites in breast milk, the effects on breastfed children, or on milk production. Due to the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 1 week after the last dose.