Lazcluze Drug Information

LAZCLUZE, in combination with amivantamab, is indicated for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.

Patient Selection

Select patients for the first-line treatment of NSCLC with LAZCLUZE, in combination with amivantamab, based on the presence of EGFR exon 19 deletions or exon 21 L858R substitution mutations in tumor or plasma specimens. If these mutations are not detected in a plasma specimen, test tumor tissue. Information on FDA-approved tests is available at: http://www.fda.gov/CompanionDiagnostics.

Recommended Dosage and Administration Recommended Dosage and Administration The recommended dosage of LAZCLUZE is 240 mg orally once daily administered in combination with amivantamab, with or without food. Swallow LAZCLUZE tablets whole. Do not crush, split, or chew.

Continue treatment until disease progression or unacceptable toxicity. Administer LAZCLUZE any time prior to amivantamab when given on the same day. Refer to the amivantamab prescribing information for recommended amivantamab dosing information.

Missed Dose If a patient misses a dose of LAZCLUZE within 12 hours, instruct patients to take the missed dose. If more than 12 hours has passed since the dose was to be given, instruct the patient to take the next dose at its scheduled time. Vomiting If vomiting occurs any time after taking LAZCLUZE, instruct the patient to take the next dose at its next regularly scheduled time.

Prophylactic and Concomitant Medications Venous Thromboembolic Events When initiating treatment with LAZCLUZE in combination with amivantamab, administer anticoagulant prophylaxis to reduce the risk of venous thromboembolic events (VTE) for the first four months of treatment. If there are no signs or symptoms of VTE during the first four months of treatment, consider discontinuation of anticoagulant prophylaxis at the discretion of the healthcare provider. Dermatologic Adverse Reactions When initiating treatment with LAZCLUZE in combination with amivantamab, prophylactic and concomitant medications are recommended to reduce the risk and severity of dermatologic adverse reactions.

Administer an oral antibiotic (doxycycline or minocycline, 100 mg orally twice daily) starting on Day 1 for the first 12 weeks of treatment. After completion of oral antibiotic treatment, administer antibiotic lotion to the scalp (clindamycin 1% topical once daily) for the next 9 months of treatment. Administer non-comedogenic skin moisturizer (ceramide-based or other formulations that provide long-lasting skin hydration and exclude drying agents) on the face and whole body (except scalp).

Wash hands and feet with 4% chlorhexidine solution once daily. Limit sun exposure during and for 2 months after treatment. Advise patients to wear protective clothing and use broad-spectrum UVA/UVB sunscreen to reduce the risk of dermatologic adverse reactions.

Dosage Modifications for Adverse Reactions

The recommended LAZCLUZE dose reductions for adverse reactions are presented in Table 1. Refer to the amivantamab prescribing information for information about dosage modifications for amivantamab. Table 2: Recommended Management and Interstitial Lung Disease (ILD)/Pneumonitis Any Grade Withhold LAZCLUZE and amivantamab if ILD/pneumonitis is suspected.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described in WARNINGS AND PRECAUTIONS and below reflect exposure to LAZCLUZE in combination with amivantamab in 421 previously untreated patients with locally advanced or metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R substitution mutations in MARIPOSA. Serious adverse reactions occurred in 49% of patients who received LAZCLUZE in combination with amivantamab.

Fatal adverse reactions occurred in 7% of patients who received LAZCLUZE in combination with amivantamab due to death not otherwise specified (1.2%); sepsis and respiratory failure (1% each); pneumonia, myocardial infarction, and sudden death (0.7% each); cerebral infarction, pulmonary embolism (PE), and COVID-19 infection (0.5% each); and ILD/pneumonitis, acute respiratory distress syndrome (ARDS), and cardiopulmonary arrest (0.2% each). Permanent discontinuation of LAZCLUZE due to an adverse reaction occurred in 21% of patients. Adverse reactions which resulted in permanent discontinuation of LAZCLUZE in ≥ 1% of patients included ILD/pneumonitis, pneumonia, VTE, rash, respiratory failure, and sudden death.

Dosage interruption of LAZCLUZE due to an adverse reaction occurred in 72% of patients. Adverse reactions which required dosage interruption in ≥ 5% of patients were rash, nail toxicity, COVID-19, VTE, increased ALT, and increased AST. Dose reductions of LAZCLUZE due to an adverse reaction occurred in 42% of patients.

Adverse reactions requiring LAZCLUZE dose reductions in ≥ 5% of patients were rash and nail toxicity. The most common adverse reactions (≥ 20%) were rash, nail toxicity, infusion-related reaction (amivantamab), musculoskeletal pain, edema, stomatitis, VTE, paresthesia, fatigue, diarrhea, constipation, COVID-19, hemorrhage, dry skin, decreased appetite, pruritus, and nausea. The most common Grade 3 or 4 laboratory abnormalities (≥ 2%) were decreased albumin, decreased sodium, increased ALT, decreased potassium, decreased hemoglobin, increased AST, increased GGT, and increased magnesium.

Table 3 summarizes the adverse reactions (≥ 10%) in MARIPOSA. Table 4 summarizes the laboratory abnormalities in MARIPOSA. Table 4: Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients with NSCLC with EGFR Exon 19 Deletion or Exon 21 L858R Substitution Mutations in MARIPOSA The denominator used to calculate the rate is the number of patients with a baseline value and at least one post-treatment value for the specific lab test.

Effect of Other Drugs on LAZCLUZE CYP3A4 Inducers

Avoid concomitant use of LAZCLUZE with strong and moderate CYP3A4 inducers. Consider an alternate concomitant medication with no potential to induce CYP3A4. Lazertinib is a CYP3A4 substrate.

Concomitant use with a strong or moderate CYP3A4 inducer decreased lazertinib concentrations, which may reduce the efficacy of lazertinib.

Effect of LAZCLUZE on Other Drugs Certain CYP3A4 Substrates Monitor for adverse reactions associated with a CYP3A4 substrate where minimal concentration changes may lead to serious adverse reactions, as recommended in the approved product labeling for the CYP3A4 substrate. Lazertinib is a weak CYP3A4 inhibitor. Concomitant use of LAZCLUZE increased concentrations of CYP3A4 substrates, which may increase the risk of adverse reactions related to these substrates.

Lazertinib is a BCRP inhibitor.

Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, LAZCLUZE can cause fetal harm when administered to a pregnant woman. There are no available data on the use of LAZCLUZE in pregnant women to inform a drug-associated risk. Oral administration of lazertinib to pregnant animals during the period of organogenesis resulted in reduced embryo-fetal survival and fetal body weight in rats and malformations in rabbits at exposures approximately 4 and 0.5 times, respectively, the human exposure at the recommended dose of 240 mg/day based on AUC (see Data ).

Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively. Lazertinib decreased fetal body weights in association with maternal toxicity at 60 mg/kg/day (approximately 4 times the human exposure at the recommended dose of 240 mg/day based on AUC).

In a dose range-finding embryo-fetal development study, oral administration of a higher dose of lazertinib (75 mg/kg/day) to pregnant rats during the period of organogenesis resulted in increased post-implantation loss. Lazertinib caused maternal toxicity (reduced body weight and food consumption leading to moribund condition and early termination) and an increase in the incidence of skeletal malformations in the vertebra and skull (fused maxillary process/zygomatic arch) at 45 mg/kg/day (approximately 0.5 times the human exposure at the recommended dose of 240 mg/day based on AUC).

Pediatric Use The safety and effectiveness of LAZCLUZE in pediatric patients have not been established.