Alipratinib Pralsetinib Capsules

I. Basic Drug Information

Generic Name: Pralsetinib

Brand Names: Pujihua, Gavreto, Alipratinib

Dosage Form & Strength: 100 mg/capsule; 60 capsules/box

Manufacturer: Lao Pharmaceutical Group Co., Ltd.

Approval Number (Lao National Drug Administration): 05 L 1102/24

Storage Conditions: 20°C–25°C (excursions permitted between 15°C–30°C); protect from light and moisture; store in original packaging (containing desiccant).

II. Indications

Requires confirmation of *RET* gene alterations via genetic testing; indicated for:

1. Non-Small Cell Lung Cancer (NSCLC):

Adult patients with locally advanced or metastatic *RET*-fusion-positive NSCLC.

2. Thyroid Cancer:

Patients aged ≥12 years with advanced or metastatic *RET*-mutant medullary thyroid cancer (MTC) requiring systemic therapy;

Patients aged ≥12 years with advanced or metastatic *RET*-fusion-positive thyroid cancer that is radioactive iodine-refractory.

III. Mechanism of Action

Target: Selective inhibitor of RET tyrosine kinase (including both wild-type and mutant forms, such as RET V804L/M and M918T).

Antitumor Mechanism: Blocks the aberrant signaling pathways of RET fusion proteins, thereby inhibiting tumor cell proliferation and survival.

Key Feature: Effective against brain metastases; capable of penetrating the blood-brain barrier.

IV. Dosage and Administration

1. Standard Dosing Regimen

Dosage: 400 mg (4 capsules) once daily, taken orally on an empty stomach (refrain from food for at least 2 hours before and 1 hour after taking the medication).

Duration of Therapy: Continue until disease progression or until intolerable toxicity occurs.

Management of Missed Doses/Vomiting:

Missed Dose: Take the missed dose as soon as possible on the same day, then resume the regular dosing schedule the following day.

Vomiting: Do not take an additional dose; resume the regular dosing schedule with the next scheduled dose. 2. Dosage Adjustment Guidelines

Table: Dose Adjustments Based on Adverse Reactions

| Type of Adverse Reaction         | Management Measures

| Interstitial Lung Disease (ILD) | Grade 1–2: Suspend → Resume at a reduced dose once resolved; Grade 3–4 or Recurrence: Permanently discontinue

| Hypertension ≥ Grade 3           | Suspend → Resume at a reduced dose once blood pressure is controlled; Refractory hypertension: Discontinue

| Hepatotoxicity (Elevated ALT/AST) | Grade 3: Suspend → Resume at a reduced dose once resolved; Grade 4 or accompanied by elevated bilirubin: Permanently discontinue

| Other Grade 3/4 Toxicities         | Suspend until ≤ Grade 1 → Stepwise dose reduction: 400 mg → 300 mg → 200 mg → 100 mg; Discontinue if still not tolerated

3. Management of Drug Interactions

| Concomitant Medication                                  | Dosage Adjustment

| Strong CYP3A4 Inhibitors (e.g., Ketoconazole) | Avoid concomitant use; if necessary, reduce dose to 200–300 mg/day

| Strong CYP3A4 Inducers (e.g., Rifampin) | Avoid concomitant use; if necessary, double dose to 800 mg/day (starting from Day 7 of concomitant use)

| Antacids / Dairy Products                           | No significant effect; no adjustment required

V. Adverse Reactions

Common Adverse Reactions (Incidence ≥ 25%)

Systemic: Fatigue (35%), Fever (20%);

Gastrointestinal: Constipation (35%), Diarrhea (34%);

Musculoskeletal: Pain (32%);

Cardiovascular: Hypertension (28%). Severe Risk Warning (Requires Immediate Intervention)

| Risk Type                     | Key Data and Management

| Interstitial Lung Disease/Pneumonia | Incidence: 10%; Grade 3–4: 2.7%; Fatal: 0.5% → Immediately discontinue medication and seek medical attention upon onset of dyspnea, cough, or fever.

| Hemorrhagic Events            | Incidence of Grade ≥3: 2.5% (including fatal cases) → Permanently discontinue medication in cases of severe hemorrhage.

| Hepatotoxicity                | Elevated AST (69%), Elevated ALT (46%); Grade 3–4: 5–6% → Monitor liver enzymes regularly.

| Impaired Wound Healing        | Discontinue medication at least 5 days prior to surgery; withhold for 2 weeks following surgery.

VI. Contraindications and Precautions

1. Pregnancy and Lactation:

Pregnant women: Absolutely contraindicated (causes fetal malformations).

Women of childbearing potential: Use effective contraception during treatment and for ≥2 weeks after discontinuing medication.

Men: Use effective contraception during treatment and for ≥1 week after discontinuing medication.

Lactation: Discontinue breastfeeding for ≥1 week after discontinuing medication.

2. Key Monitoring Requirements:

Blood Pressure: Optimize prior to treatment; monitor during the first week and monthly thereafter.

Liver Enzymes: Monitor AST/ALT every 2 weeks for the first 3 months, then monthly thereafter.

Pulmonary Symptoms: Regularly assess for dyspnea and cough.

3. Special Populations:

Patients with Hepatic Impairment: No dose adjustment required for mild impairment; contraindicated in moderate to severe impairment.

Pediatric Patients: Indicated only for thyroid cancer in patients aged ≥12 years. VII. Clinical Efficacy Data

Results from the Key ARROW Trial:

| Patient Type                         | Overall Response Rate (ORR) | Median Duration of Response (DOR)

| Treatment-naïve RET-fusion NSCLC (27 patients) | 70% (CR 11%)                | 9.0 months

| Previously treated RET-fusion NSCLC (87 patients) | 57% (CR 5.7%)               | >15.2 months

| Patients with Brain Metastases (8 patients with measurable lesions) | 50% (CR 25%)                | >6 months (75% of patients)

Note: Effective in patients resistant to PD-1/PD-L1 therapy (ORR 59%).

Disclaimer: The information above is compiled based on the product prescribing information and clinical studies. Specific medication use must strictly adhere to a physician's instructions, and regular monitoring of blood pressure, liver enzymes, and pulmonary symptoms is required.