BIGBEAR CAMPAMDX Capmatinib

I. Basic Drug Information

Generic Name: Capmatinib

Brand Name: Tabrecta / CAMPAMDX

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

Dosage Form & Strength: 200 mg/tablet; 56 tablets/box

Target: MET Receptor Tyrosine Kinase

Laos National Drug Administration Registration No.: 04L 0962/23

II. Indications

Indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring a confirmed MET exon 14 skipping mutation (METex14). It is applicable to the following two patient populations:

1. Treatment-naïve patients: Those who have not received prior systemic therapy;

2. Previously treated patients: Those whose disease has progressed following prior platinum-based chemotherapy or immunotherapy.

III. Pharmacological Action

Mechanism of Action: Highly selective inhibition of MET receptor tyrosine kinase; blocks the aberrant activation of the MET signaling pathway; inhibits tumor cell proliferation, metastasis, and immune evasion.

Key Feature: Demonstrates significant penetration of the blood-brain barrier and is effective in patients with brain metastases.

IV. Dosage and Administration

1. Standard Dosing Regimen

| Item          | Recommended Regimen

| Dose          | 400 mg, twice daily (2 tablets of 200 mg per dose, or an equivalent combination)

| Administration | Swallow tablets whole; may be taken with or without food; maintain a fixed interval of approximately 12 hours (e.g., 8:00 AM and 8:00 PM)

| Duration      | Continue until disease progression or the occurrence of intolerable toxicity

2. Dosage Adjustments for Special Populations

Hepatic Impairment:

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

Severe (Child-Pugh Class C): Use with caution; safety has not been established.

Elderly Patients (≥ 65 years): No dosage adjustment required, but increased monitoring is recommended.

3. Management of Missed Doses or Vomiting

Missed Dose: If more than 6 hours remain before the next scheduled dose, take the missed dose immediately; otherwise, skip the missed dose. Do not take a double dose to make up for a missed one. Vomiting after taking the medication: Skip the missed dose and take the next scheduled dose as planned.

4. Dose Adjustments (for Adverse Reactions)

| Type of Toxicity                                      | Management Measures

| ≥ Grade 3 Hepatotoxicity (ALT/AST > 5 × ULN) | Suspend treatment → Resume once recovered to ≤ Grade 1 → Restart at a reduced dose of 200 mg twice daily → Permanently discontinue if toxicity recurs

| ≥ Grade 3 Non-hepatic Toxicity (e.g., edema, rash)     | Suspend treatment → Resume once recovered at a reduced dose level (400 mg → 200 mg → 150 mg)

| Interstitial Lung Disease (ILD) / Pneumonitis                | Permanently discontinue treatment; immediately initiate corticosteroid therapy

V. Adverse Reactions

Common Adverse Reactions (≥ 20%)

| Type          | Specific Manifestations                                   | Incidence

| Systemic       | Peripheral edema (swelling of hands/feet), fatigue     | 53%–83%

| Gastrointestinal       | Nausea, vomiting, diarrhea, decreased appetite      | 28%–44%

| Respiratory    | Dyspnea, cough                         | 20%–35%

| Laboratory Abnormalities | Lymphopenia, elevated AST/ALT, hypoalbuminemia | 25%–58%

Serious Adverse Reactions

1. Interstitial Lung Disease (ILD) / Pneumonitis:

Incidence: 0.8%–3%; potentially fatal.

Management: Immediately suspend treatment and investigate upon the onset of new dyspnea, cough, or fever; permanently discontinue treatment if confirmed.

2. Hepatotoxicity:

Monitoring Requirements: Monitor liver function every 2 weeks during the first 3 months of treatment, then once monthly thereafter.

3. Photosensitivity Reactions:

Avoid exposure to ultraviolet (UV) light; use sunscreen and/or protective clothing.

VI. Contraindications

1. Hypersensitivity to capmatinib or any of its excipients;

2. Active ILD or pneumonitis;

3. Pregnancy and lactation (poses a risk to the fetus; breastfeeding is contraindicated for at least 1 week after discontinuing the medication). VII. Precautions

1. Liver Function Monitoring: Baseline levels of ALT, AST, and bilirubin should be measured, and periodic monitoring conducted throughout treatment.

2. Drug Interactions:

Strong CYP3A4 Inducers (e.g., Rifampin): Avoid concomitant use (may decrease Capmatinib plasma concentrations).

P-gp Substrates (e.g., Digoxin): Monitor plasma concentrations when used concomitantly.

3. Contraception: Patients of reproductive potential must use effective contraception during treatment and for at least one week after discontinuing the medication.

VIII. Use in Specific Populations

Pediatric Patients: Safety has not been established; use is not recommended.

Geriatric Patients: No dose adjustment is required; however, increased monitoring for comorbidities is recommended.

Hepatic/Renal Impairment:

Mild to Moderate Hepatic Impairment: No dose adjustment required.

Severe Hepatic or Renal Impairment: Data are limited; use with caution.

IX. Storage and Packaging

Storage: Store in the original container, protected from light, at 20°C–25°C (excursions permitted between 15°C–30°C).

After Opening: Discard any unused medication within 6 weeks of first opening the bottle.

Summary

Capmatinib is the world's first highly selective METex14 inhibitor, offering precision therapy for specific patients with non-small cell lung cancer (NSCLC). Administration guidelines include:

Confirmation of METex14 mutations via genetic testing;

Fixed oral dosage of 400 mg twice daily; tablets must be swallowed whole;

Close monitoring of liver function and pulmonary symptoms, with prompt management of ILD/hepatotoxicity;

Mandatory contraception for patients of reproductive potential, and avoidance of UV exposure.