BIGBEAR SOTOLDX Sotorasib sotoldx

I. Basic Drug Information

Generic Name: Sotorasib

Brand Name: Lumakras / SOTOLDX

Development Code: AMG-510

Manufacturer: BigBear Pharmaceutical Co., Ltd. (Laos)

Dosage Form & Strength: 120 mg/tablet; 56 tablets/box

Laos National Drug Administration Registration No.: 05L 0978/23

II. Indications

Indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring a *KRAS* G12C mutation, as detected by an FDA-approved test, who have received at least one prior systemic therapy (such as platinum-based chemotherapy or immunotherapy).

III. Dosage and Administration

1. Standard Dosing Regimen

| Item          | Recommended Regimen

| Dose          | 960 mg (8 tablets) once daily, orally

| Administration Time | At a fixed time each day; may be taken with or without food

| Duration of Treatment | Continue until disease progression or until intolerable toxicity occurs

2. Dosage Adjustments for Special Populations

Patients with Dysphagia (Difficulty Swallowing):

Disperse 8 tablets (960 mg) in 120 mL of non-carbonated, room-temperature water; stir until dispersed (the tablets will not dissolve completely), and drink within 2 hours.

Rinse the container with an additional 120 mL of water and drink the rinse.

Hepatic Impairment:

Mild to Moderate Impairment (Child-Pugh Class A/B): No dosage adjustment required.

Severe Impairment (Child-Pugh Class C): Safety has not been established; use with caution.

3. Management of Missed Doses or Vomiting

Missed dose < 6 hours: Take the missed dose as soon as possible.

Missed dose ≥ 6 hours, or vomiting occurs after administration: Skip the missed dose and resume the regular schedule the next day; do not take a double dose to make up for the missed dose. 4. Dosage Adjustment (for Adverse Reactions)

| Toxicity Grade                                              | Management Measures

| Grade ≥3 Hepatotoxicity (ALT/AST > 5 × ULN) | Suspend treatment → Once resolved to Grade ≤1 → Resume at a reduced dose of 480 mg/day → If toxicity recurs, further reduce to 240 mg/day

| Grade ≥3 Non-hepatic Toxicity (e.g., diarrhea, rash) | Suspend treatment → Once resolved to Grade ≤1 → Resume at a reduced dose level (960 mg → 480 mg → 240 mg)

| Interstitial Lung Disease (ILD)/Pneumonitis | Permanently discontinue treatment, and initiate corticosteroid therapy

Minimum Tolerated Dose: 240 mg/day; if still unable to tolerate, permanently discontinue treatment.

IV. Warnings and Precautions

1. Hepatotoxicity

Incidence: 18% of patients experienced elevated AST/ALT levels (6.6% were Grade ≥3); the median time to onset was 9 weeks.

Monitoring Requirements:

During the first 3 months of treatment: Monitor ALT/AST/Total Bilirubin every 3 weeks;

After 3 months: Monitor monthly; increase monitoring frequency if abnormalities are detected.

2. Interstitial Lung Disease (ILD)/Pneumonitis

Incidence: 0.8% (all cases were Grade 3–4); the median time to onset was 2 weeks, with 1 reported death.

Management: Immediately suspend treatment upon the onset of new or worsening dyspnea, cough, or fever; permanently discontinue treatment once a definitive diagnosis is established. 3. Drug Interactions

| Concomitant Drug                                   | Recommended Adjustment

| Proton Pump Inhibitors (PPIs)                 | Avoid concomitant use; if necessary, administer Sotorasib 4 hours before or 10 hours after the PPI.

| Strong CYP3A4 Inducers (e.g., Rifampin) | Avoid concomitant use (AUC ↓ 51%); if necessary, monitor for reduced efficacy.

| P-gp Substrates (e.g., Digoxin)               | Monitor digoxin concentrations during concomitant use (Sotorasib ↑ its AUC by 21%).

V. Adverse Reactions

Common Adverse Reactions (≥20%)

Systemic: Fatigue (45%), Musculoskeletal pain (32%);

Gastrointestinal: Diarrhea (31%), Nausea (28%);

Hepatobiliary: Hepatotoxicity (18%; AST/ALT ↑);

Respiratory: Cough (20%).

Laboratory Abnormalities (≥25%)

| Parameter         | Abnormality Rate    | Rate of Grade ≥3

| Lymphopenia (↓) | 73%                 | 10%

| AST Elevation (↑) | 58%                 | 6%

| Hemoglobin Decrease (↓) | 53%                 | 8%

| Hypocalcemia (↓)      | 49%                 | 2%

Serious Adverse Reactions

Fatal: Pneumonia (8%), Hepatic failure (3.4%), Respiratory failure (0.8%).

Leading Causes of Discontinuation: Hepatotoxicity (4.9%), ILD (0.6%).

VI. Contraindications

1. Hypersensitivity to Sotorasib or any of its excipients;

2. Active ILD/Pneumonitis;

3. Pregnancy and Lactation (although animal studies showed no embryotoxicity, human data are lacking).

VII. Use in Specific Populations

Pregnancy/Lactation:

Pregnancy Category: No data available (animal studies were negative, but human risk is unknown); effective contraception is required during treatment.

Lactation: Breastfeeding is prohibited for 1 week after discontinuing the drug.

Pediatric Patients: Safety has not been established; use is not recommended. Elderly Patients (≥65 years): No dose adjustment is required; however, increased monitoring is recommended due to the risk of comorbidities.

VIII. Storage and Packaging

Storage: 20°C–25°C (excursions permitted between 15°C–30°C); protect from light and moisture; do not freeze.

Packaging: 120 mg/tablet; 56 tablets/box.

IX. Clinical Efficacy Data

Objective Response Rate (ORR): 36% (Complete Response: 2%; Partial Response: 35%);

Median Duration of Response (DoR): 10.0 months (58% of patients maintained a response for ≥6 months);

Median Progression-Free Survival (PFS): 6.8 months.

Summary

Sotorasib is the world's first KRAS G12C inhibitor, offering a breakthrough treatment option for specific patients with non-small cell lung cancer (NSCLC). Administration guidelines include:

Confirmation of the KRAS G12C mutation via genetic testing;

Fixed oral dosage of 960 mg once daily; avoid co-administration with acid-reducing agents;

Close monitoring of liver function and pulmonary symptoms, with timely dose adjustments as needed.

How to Choose: Sotorasib, Fuzerece Tablets, Gesorece Tablets, or Adagrasib?

Sotorasib, Adagrasib, Fuzerece Tablets, and Gesorece Tablets are all KRAS G12C-targeted therapies primarily used to treat non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation. However, they differ in various aspects, including whether they are original brand-name or domestically produced drugs, their respective development companies, market launch status, and clinical efficacy data. Key Differences Among the Three

Sotorasib: Developed by Amgen (USA); the world's first KRAS G12C inhibitor; backed by mature clinical data; carries a high price tag.

Adagrasib: Developed by Mirati Therapeutics (USA); often the preferred choice for patients with brain metastases; carries a relatively high price tag.

Fuzeresib Tablets: Developed by Innovent Biologics (China); positioned as a domestic alternative; supported by moderately mature clinical data; eligible for medical insurance reimbursement.

Gesoresib Tablets: Jointly developed by Chia Tai Tianqing and InventisBio (China); supported by relatively early-stage clinical data.

I. If Prioritizing "Efficacy Above All Else"

Priority Choice: Adagrasib

Currently, many oncologists believe that Adagrasib demonstrates slightly stronger overall activity compared to Sotorasib.

It performs particularly well in cases involving brain metastases, progression-free survival (PFS), and achieving deep clinical responses.

In certain studies, it has demonstrated a higher Objective Response Rate (ORR), longer PFS, and superior control over central nervous system (CNS) metastases.

Consequently—especially for patients with brain metastases—there is a growing trend among clinicians to favor Adagrasib.

II. If Prioritizing "Stability, Safety, and Maturity"

Priority Choice: Sotorasib

This was the world's first targeted therapy specifically designed for KRAS G12C mutations.

Advantages: It boasts the most extensive global clinical experience, is the most familiar to physicians, offers a more stable safety profile, and is associated with relatively milder side effects.

Some analyses suggest that while Adagrasib may offer slightly stronger efficacy, Sotorasib demonstrates superior tolerability.

Therefore: For patients who are elderly, have compromised liver function, or are physically frail, many physicians will—conversely—opt to consider Sotorasib first.

III. If Budget Is Limited

Domestic Drugs Offer a Distinct Advantage: Gesoresib Tablets and Fuzeresib Tablets

Typically: These options feature lower costs, offer more convenient access via domestic distribution channels, and are eligible for medical insurance reimbursement—thereby significantly alleviating financial burdens for many patients.

However, a realistic challenge remains: Data regarding real-world long-term outcomes, international Phase III trials, and large-scale drug resistance patterns...

...are currently not as mature or extensive as those available for Sotorasib and Adagrasib. IV. Current Real-World Trends in the Field

The prevailing trends in clinical practice have become increasingly evident:

For standard second-line therapy, Sotorasib is the more common choice.

For patients seeking superior therapeutic efficacy, Adagrasib is the more common choice.

For patients with brain metastases, Adagrasib is the more common choice.

For those with limited budgets, domestically produced medications are the more common choice.