I. Basic Information

Generic Name: Pralsetinib

Brand Names: Pujihua, Gavreto, PRASEDX

Target: RET (Rearranged during Transfection) Kinase Inhibitor

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

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

Approval Number (Laos National Drug Administration): 07L 1157/24

Storage Conditions: Room temperature (20°C–25°C); protect from light and moisture; short-term storage at 15°C–30°C is permitted.

II. Indications

1. RET Fusion-Positive Non-Small Cell Lung Cancer (NSCLC)

In adult patients with locally advanced or metastatic disease.

2. RET-Mutant Medullary Thyroid Carcinoma (MTC)

In advanced/metastatic patients (aged ≥12 years) requiring systemic therapy.

3. RET Fusion-Positive Thyroid Cancer

In advanced/metastatic patients (aged ≥12 years) who are radioactive iodine-refractory.

Prior to administration, the presence of RET gene alterations must be confirmed by a test approved by the FDA or NMPA.

III. Dosage and Administration

# Dosing Regimen

Standard Dose: 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 dose).

Treatment Duration: Continue treatment until disease progression or until intolerable toxicity occurs.

# Management of Special Situations

| Scenario | Management

| Missed Dose | Take the missed dose as soon as possible on the same day; if it is close to the time for the next scheduled dose (<4 hours), skip the missed dose and do not take a double dose.

| Vomiting | Do not take a replacement dose; continue with the next scheduled dose as planned.

Dose Adjustments (Based on Adverse Reactions)

First Dose Reduction: 300 mg/day → Second Dose Reduction: 200 mg/day → Third Dose Reduction: 100 mg/day. Permanent Discontinuation: Intolerance to 100 mg/day, or occurrence of any of the following:

Grade 3–4 Interstitial Lung Disease (ILD) or recurrence;

Grade 4 Hypertension / Hepatotoxicity / Hemorrhagic Events.

#Dose Adjustments for Drug Interactions

| Concomitant Medication | Dose Adjustment

| Strong CYP3A4/P-gp Inhibitors (e.g., Itraconazole) | Reduce dose to 200 mg/day (from 400 mg) or 100 mg/day (from 300/200 mg).

| Strong CYP3A4 Inducers (e.g., Rifampin) | Double the dose starting from Day 7 of concomitant use; resume original dose 14 days after discontinuing the inducer.

IV. Management of Adverse Reactions

Common Adverse Reactions (≥25%)

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

Metabolic/Musculoskeletal: Hypertension (28%), Musculoskeletal Pain (32%);

Gastrointestinal: Constipation (35%), Diarrhea (24%).

#Management of Severe Toxicities

| Toxicity Type | Monitoring and Intervention Measures

| ILD/Pneumonitis | Incidence: 10% (Grade 3–4: 2.7%); immediately discontinue the drug and perform imaging studies upon the onset of cough, dyspnea, or fever.

| Hypertension | Control blood pressure prior to treatment; monitor weekly during the first week and monthly thereafter; for Grade 3, suspend treatment + initiate antihypertensive therapy, then resume at a reduced dose; for Grade 4, permanently discontinue the drug.

| Hepatotoxicity | Monitor AST/ALT every 2 weeks for the first 3 months, then monthly thereafter; for Grade 3–4, suspend treatment and reduce the dose; permanently discontinue the drug if toxicity recurs.

| Hemorrhagic Events | Permanently discontinue the drug for bleeding events of Grade 3 or higher (fatal cases have been reported).

V. Contraindications and Warnings

Perioperative Management: Discontinue the drug ≥5 days prior to elective surgery; resume ≥2 weeks after major surgery (once wound healing is established). Embryo-Fetal Toxicity: Contraindicated in pregnant women. Patients of reproductive potential and their partners must use contraception during treatment and for a specified period following the last dose:

Females: Use non-hormonal contraception until 2 weeks after discontinuing the drug;

Males: Use contraception until 1 week after discontinuing the drug.

Lactation: Breastfeeding is prohibited during treatment and for 1 week following the last dose.

VI. Clinical Efficacy (Key Study: ARROW)

| Patient Population | Efficacy Endpoint | Results

| Treatment-naïve RET-fusion NSCLC (n=27) | Overall Response Rate (ORR) | 70% (CR 11%, PR 59%)

| Previously treated RET-fusion NSCLC (n=87) | ORR / Median Duration of Response (DoR) | 57% / Not reached (>15.2 months)

| Patients with Brain Metastases (n=8) | Intracranial ORR | 50% (2 CRs, 2 PRs)

VII. Use in Specific Populations

Hepatic Impairment: No dose adjustment required for mild impairment (bilirubin ≤ 1.5 × ULN); no data available for moderate to severe impairment—use with caution.

Renal Impairment: No dose adjustment required for mild to moderate impairment; no data available for severe impairment (CrCl < 15 mL/min).

Pediatric Patients: For patients ≥ 12 years of age, use adult dosing; safety has not been established for patients < 12 years of age.

VIII. Pharmacology and Pharmacokinetics

Mechanism of Action: Highly selective inhibition of RET kinase, blocking tumor proliferation signals.

Pharmacokinetic Parameters:

Time to Peak Concentration (Tmax): 2–4 hours (fasted state); food increases AUC by 122% — must be taken in a fasted state;

Half-life: 14.7 hours (single dose) → 22.2 hours (steady state);

Metabolism: Primarily via CYP3A4; elimination is predominantly via feces (>80%).

IX. Patient Counseling Information

Dietary Restrictions: Avoid grapefruit (inhibits CYP3A4). Monitoring Requirements:

- Blood pressure (once monthly, starting from Week 1);

- Liver function (every 2 weeks for the first 3 months, then once monthly thereafter);

- Respiratory symptoms (promptly report any cough or shortness of breath).

The information above synthesizes data from the product prescribing information and the ARROW study; specific treatment regimens must be determined by an oncologist based on RET testing results and patient tolerability.

Product Specifications

Product Name: BigBear Pralsetinib Capsules 100mg (60 capsules/box) — BIGBEAR PRASEDX Pralsetinib

Common Name: Pralsetinib Capsules

Active Ingredient: Pralsetinib

Dosage Form: Capsules

Specification: 100 mg/capsule; 60 capsules/box

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

Indications:

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

In adult patients with locally advanced or metastatic disease.

2. RET-mutant Medullary Thyroid Carcinoma (MTC):

In patients (aged ≥12 years) with advanced or metastatic disease requiring systemic therapy.

3. RET fusion-positive Thyroid Cancer:

In patients (aged ≥12 years) with advanced or metastatic disease that is refractory to radioactive iodine.

Prior to initiation of treatment, the presence of RET gene alterations must be confirmed via an FDA- or NMPA-approved diagnostic test.

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