Lazertinib (Trade Names: LECLAZA/Lazcluze) Detailed Prescribing Information

Product Name: Lazertinib Tablets

Other Chinese Names: Lanzetinib

English Name: Lazertinib Tablets

Trade Names: LECLAZA / Lazcluze / LuciLazer

Specification: 80 mg/tablet; 60 tablets/box.

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

Laos National Drug Approval Number: 03 L 1326/25

I. Indications

1. EGFR-Mutation Positive Non-Small Cell Lung Cancer (NSCLC)

Monotherapy: Indicated for patients with locally advanced or metastatic NSCLC harboring the EGFR T790M mutation who have progressed following prior treatment with an EGFR-TKI (based on approval by the Korean MFDS in 2021).

Combination Therapy: In combination with amivantamab, indicated as a first-line treatment for patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations (approved by the FDA in 2024).

II. Dosage and Administration

1. Recommended Dosage

Monotherapy: 240 mg orally once daily. May be taken with or without food. Swallow the tablet whole.

Combination Therapy: 240 mg once daily, in combination with amivantamab (amivantamab should be administered via intravenous infusion at its recommended dosage).

2. Dosage Adjustments

Missed Dose: If a dose is missed by less than 12 hours, take the missed dose as soon as possible; if more than 12 hours have elapsed, skip the missed dose.

Dosage Adjustments for Adverse Reactions:

Interstitial Lung Disease (ILD): Permanently discontinue treatment.

Grade 3 or Higher Toxicity: Suspend treatment for 3 weeks; upon recovery, reduce the dose to 160 mg. If the patient remains intolerant, permanently discontinue treatment. III. Adverse Reactions

1. Common Adverse Reactions (≥20%)

Rash (44.9%), pruritus (33.3%), paresthesia (32.1%), muscle spasms (25.6%), headache (24.4%), diarrhea (21.8%), decreased appetite (20.5%).

2. Serious Adverse Reactions

Interstitial pneumonia (1.2%), hepatotoxicity (elevated ALT/AST; 7.2%), QTc interval prolongation (3.3%), venous thromboembolism (VTE; 36% when used in combination therapy).

3. Laboratory Abnormalities

Elevated ALT/AST (7.2%), neutropenia, hyperglycemia, etc.

IV. Contraindications

There are no specific contraindications; however, the drug is contraindicated in patients with a known hypersensitivity to any of its components.

V. Precautions

1. Monitoring of Hepatic and Renal Function

Monitor hepatic function (ALT/AST) and renal function periodically prior to and during treatment; a dose reduction is required for patients with moderate to severe hepatic impairment.

2. Interstitial Lung Disease (ILD)

Discontinue the drug immediately and conduct an evaluation if symptoms such as dyspnea, cough, or fever occur.

3. Cardiovascular Risk

Monitor the QTc interval and avoid concomitant use with other medications known to prolong the QTc interval.

4. Embryo-Fetal Toxicity

Contraindicated in pregnant women; women of reproductive potential must use effective contraception for at least 3 weeks after discontinuing the drug.

5. Cutaneous and Ocular Toxicity

Use sunscreens and moisturizers to prevent skin reactions; refer patients to an ophthalmologist if symptoms of keratitis occur.

VI. Drug Interactions

1. CYP3A4 Inhibitors/Inducers:

Inhibitors (e.g., ketoconazole) may increase plasma concentrations of lazertinib; monitor for signs of toxicity.

Inducers (e.g., rifampin) may reduce therapeutic efficacy; concomitant use should be avoided.

2. BCRP/CYP3A4 Substrates:

Avoid concomitant use with drugs such as rosuvastatin or midazolam, as this may increase the exposure to these substrates. VII. Pharmacological Mechanisms

Target: Irreversibly inhibits EGFR-sensitizing mutations (Del19, L858R) and the T790M resistance mutation, while sparing wild-type EGFR activity.

Blood-Brain Barrier Penetration: Effective in patients with brain metastases, demonstrating an intracranial objective response rate of 55%.

VIII. Storage

Storage: Store in a tightly sealed container, protected from light, at room temperature (15–30°C).

IX. Clinical Data

1. Monotherapy Efficacy (Second-line Treatment):

Objective Response Rate (ORR) of 58%; Median Progression-Free Survival (mPFS) of 11.0 months.

2. Combination Therapy (First-line):

The MARIPOSA trial demonstrated that the combination therapy arm (with amivantamab) achieved an mPFS of 23.7 months, which was significantly superior to osimertinib (16.6 months).