Lazertinib, a third-generation EGFR TKI (tyrosine kinase inhibitor), is used to treat NSCLC (non-small cell lung cancer) with specific EGFR mutations, especially when resistance to first- and second-generation TKIs develops. It's often used in combination with amivantamab, and experts advise careful consideration of potential side effects and drug interactions.

Lucilazer is a kinase inhibitor indicated in combination with amivantamab for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have an epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutation as detected by an FDA-approved test.

240 mg PO qDay plus amivantamab (dose based on baseline body weight) until disease progression or unacceptable toxicity.

Locally advanced or metastatic non-small cell lung cancer (NSCLC) who have an epidermal growth factor receptor (EGFR).

Lazertinib is an epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET) targeted bispecific antibody that has been designed to recognize and attach to specific targets in the body. It targets two proteins found in cancer cells. It works by attaching to these proteins and may help to slow or stop your lung cancer from growing. It may also reduce the size of the tumor. 

Irreversible, mutant-selective, third-generation epidermal growth factor receptor (EGFR) inhibitor.

Blocking EGRF results in inhibition of tumor cell proliferation and survival.

EGFR exon 19 deletions and exon 21 L858R substitution mutations were inhibited at lower concentrations than wild-type EGFR.

Antitumor activity was demonstrated in human NSCLC cells and mouse xenograft models of EGFR exon 19 deletions or EGFR L858R substitution mutations.

Combination therapy with lazertinib plus amivantamab increased in vivo antitumor activity compared with either agent alone in mouse xenograft models of human NSCLC with EGFR L858R mutation.

Oral Administration

May take with or without food.

Swallow tablets whole; do not crush, split, or chew.

Administer any time before amivantamab when given on the same day.

Missed dose

Within 12 hr of scheduled time: Administer missed dose.

>12 hr after scheduled time: Skip dose and take next dose at regularly scheduled time.

Vomiting after dose

Do not take an extra dose.

Take the next dose at the regularly scheduled time.

Lucilazer combined with Amivantamab

The most common adverse reactions (≥ 20%) included

Rash

Nail toxicity

Infusion-related reactions (amivantamab)

Musculoskeletal pain

Edema

Stomatitis

Venous Thromboembolism (VTE)

Paresthesia

Fatigue

Diarrhea

Constipation

COVID-19

Hemorrhage

Dry skin

Decreased appetite

Pruritus

Nausea

Ocular toxicity

The most common grade 3 or 4 laboratory abnormalities (≥ 2%) included

Decreased albumin

Decreased sodium

Increased alanine aminotransferase (ALT)

Decreased potassium

Decreased hemoglobin

Increased aspartate aminotransferase (AST)

Increased glutamyl transpeptidase (GGT)

Increased magnesium

• Venous Thromboembolic Events (VTE): Prophylactic anticoagulation is recommended for the first four months of treatment. Monitor for signs and symptoms of VTE and treat as appropriate. Withhold Lucilazer and amivantamab based on severity. After initiating anticoagulation, resume Lucilazer and amivantamab at the same doses as recommended by your healthcare provider. If VTE recurs, permanently discontinue amivantamab and continue LuciLazer, even with therapeutic anticoagulation.

• Interstitial Lung Disease (ILD)/Pneumonitis: Monitor for new or worsening symptoms of ILD/pneumonitis. Withhold Lucilazer and amivantamab in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.

• Skin adverse reactions: Severe rash, including acneiform dermatitis, may occur. Advise patients to use an alcohol-free moisturizer and encourage them to reduce sun exposure during treatment and for 2 months after treatment to reduce the risk of skin reactions. Based on severity, withhold, reduce the dose, or permanently discontinue LuciLazer and amivantamab.

• Ocular Adverse Reactions: Patients who develop new or worsening signs and symptoms of ocular adverse reactions, including keratitis, should be promptly referred to an ophthalmologist for evaluation. Based on severity, withhold or reduce the dose or permanently discontinue amivantamab and continue LuciLazer.

• Embryo-fetal toxicity: May cause harm to the fetus. Advise patients of reproductive potential to be aware of the potential risk to the fetus and to use effective contraceptive measures.

Store at room temperature at 20-25ºC (68-77ºF)

Excursions permitted between 15-30ºC (59-86ºF)

Regular monitoring for adverse events and disease progression is crucial during lazertinib treatment. 

Ongoing clinical trials are exploring the use of lazertinib in various combinations and in patients with uncommon EGFR mutations. 

Advise pregnant patients of potential risk to a fetus. Perform pregnancy testing before initiation in females of reproductive potential.