Source: European Medicines Agency (EU) Revision Year: 2025 Publisher: Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium
Lazcluze in combination with amivantamab is indicated for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R substitution mutations.
Treatment with Lazcluze should be initiated by a physician experienced in the use of anticancer medicinal products.
Before initiation of Lazcluze, EGFR mutation-positive status in tumour tissue or plasma specimens must be established using a validated test method. If no mutation is detected in a plasma specimen, tumour tissue should be tested if available in sufficient amount and quality due to the potential for false negative results using a plasma test.
The recommended dose of Lazcluze is 240 mg once daily in combination with amivantamab.
It is recommended to administer Lazcluze any time prior to amivantamab when given on the same day. Refer to section 4.2 of the amivantamab Summary of Product Characteristics for recommended amivantamab dosing information.
At the initiation of treatment, prophylactic anticoagulants should be administered to prevent venous thromboembolic (VTE) events in patients receiving Lazcluze in combination with amivantamab. Consistent with clinical guidelines, patients should receive prophylactic dosing of either a direct acting oral anticoagulant (DOAC) or a low molecular weight heparin (LMWH). Use of Vitamin K antagonists is not recommended.
Patients should be instructed to limit sun exposure during and for 2 months after Lazcluze combination therapy and alcohol-free emollient cream is recommended for dry areas. For further information about prophylaxis for skin and nail reactions, see section 4.4.
Treatment should continue until disease progression or unacceptable toxicity.
If a planned dose of Lazcluze is missed, it can be administered within 12 hours. If more than 12 hours have passed since the dose was to be given, the missed dose should not be administered and the next dose should be administered per the usual dosing schedule.
The recommended dose reductions for adverse reactions are presented in Table 1.
Table 1. Recommended Lazcluze dose reductions for adverse reactions:
| Dose reduction | Recommended dose |
|---|---|
| Initial dose | 240 mg once daily |
| 1st dose reduction | 160 mg once daily |
| 2nd dose reduction | 80 mg once daily |
| 3rd dose reduction | Discontinue Lazcluze |
Dose modifications for specific adverse reactions are presented in Table 2.
Refer to section 4.2 of the amivantamab Summary of Product Characteristics for information about dose modifications for amivantamab.
Table 2. Recommended Lazcluze and amivantamab dose modifications for adverse reactions*:
| Adverse reaction | Severity | Dose modification |
|---|---|---|
| Interstitial lung disease (ILD)/pneumonitis | Any grade | • Withhold Lazcluze and amivantamab if ILD/pneumonitis is suspected. • Permanently discontinue Lazcluze and amivantamab if ILD/pneumonitis is confirmed. |
| Venous thromboembolic (VTE) events (see section 4.4) | Events with clinical instability (e.g., respiratory failure or cardiac dysfunction) | • Withhold Lazcluze and amivantamab until the patient is clinically stable. Thereafter, both medicinal products can be resumed at the same dose. |
| Recurrent VTE event despite therapeutic level anticoagulation | • Permanently discontinue amivantamab. Treatment can continue with Lazcluze at the same dose. | |
| Skin and nail reactions (see section 4.4) | Grade 1 | • Supportive care should be initiated. • Reassess after 2 weeks. |
| Grade 2 | • Supportive care should be initiated. • If there is no improvement after 2 weeks, reduce amivantamab dose and continue Lazcluze. • Reassess every 2 weeks, if no improvement, reduce Lazcluze dose until ≤ Grade 1 (Table 1). | |
| Grade 3 | • Supportive care should be initiated. • Withhold Lazcluze and amivantamab. • Upon recovery to ≤ Grade 2, resume both medicinal products at the same dose or consider dose reduction, preferentially reducing the dose of amivantamab first. • If there is no improvement within 2 weeks, permanently discontinue both Lazcluze and amivantamab. | |
| Grade 4 (including severe bullous, blistering or exfoliating skin conditions, e.g., Toxic epidermal necrolysis) | • Permanently discontinue amivantamab and hold Lazcluze. • Withhold Lazcluze until ≤ Grade 2 or baseline. • Upon recovery to ≤ Grade 2, resume Lazcluze at the same dose. | |
| Hepatotoxicity | Grade 3-4 | • Withhold Lazcluze and amivantamab. • Upon recovery to ≤ Grade 1, resume both medicinal products at the same dose or consider dose reduction, preferentially reducing the dose of amivantamab first. |
| Paraesthesia | Grade 3-4 | • Supportive care should be initiated. • Withhold Lazcluze until ≤ Grade 1 or baseline. Resume Lazcluze at the same dose or consider dose reduction. • Consider permanently discontinuing Lazcluze if recovery does not occur within 4 weeks. |
| Diarrhoea | Grade 3 | • Supportive care should be initiated. • Withhold Lazcluze and amivantamab. • Upon recovery to ≤ Grade 1, resume both medicinal products at the same dose or consider dose reduction, preferentially reducing the dose of amivantamab first. |
| Grade 4 | • Supportive care should be initiated. • Withhold Lazcluze and amivantamab. • Upon recovery to ≤ Grade 1, reduce the dose, preferentially reducing the dose of amivantamab first. | |
| Stomatitis | Grade 3-4 | • Withhold Lazcluze and amivantamab. • Upon recovery to ≤ Grade 2, resume both medicinal products at the same dose or consider dose reduction, preferentially reducing the dose of amivantamab first. |
| Other adverse reactions | Grade 3-4 | • Withhold Lazcluze and amivantamab until the adverse reaction resolves to ≤ Grade 1 or baseline. • Resume one or both medicinal products, preferentially resuming Lazcluze first at a reduced dose, unless the adverse reaction is strongly suspected to be related to Lazcluze. • Consider permanently discontinuing both Lazcluze and amivantamab if recovery does not occur within 4 weeks. |
* Refer to section 4.2 of the amivantamab Summary of Product Characteristics for recommended amivantamab dosing information.
No dose adjustment is required (see sections 4.8, 5.1 and 5.2).
Based on population pharmacokinetics (PK) analysis, no dose adjustment is required for patients with mild, moderate or severe renal impairment. Data in patients with severe renal impairment are limited. The PK of lazertinib in patients with end stage renal disease is unknown. Caution is required in patients with end-stage renal disease (see section 5.2).
No dose adjustment is required for patients with mild or moderate hepatic impairment. The PK of lazertinib in patients with severe hepatic impairment is unknown. Caution is required in patients with severe hepatic impairment (see section 5.2).
There is no relevant use of lazertinib in the paediatric population for the treatment of non-small cell lung cancer.
Lazcluze is for oral use. The tablets should be swallowed whole with or without food. Tablets should not be crushed, split, or chewed.
If vomiting occurs any time after taking Lazcluze, the next dose should be taken the next day.
There is no known specific antidote for Lazcluze overdose. In the event of an overdose, stop Lazcluze and undertake general supportive measures. Patients should be closely monitored for signs or symptoms of adverse reactions.
2 years.
This medicinal product does not require any special storage conditions.
Lazcluze 80 mg film-coated tablets:
Blister pack:
Polyvinyl chloride – polychlorotrifluoroethylene (PVC-PCTFE) film and aluminium push-through foil.
Bottle:
White opaque high-density polyethylene (HDPE) bottle with polypropylene child-resistant closure containing either 60 or 90 tablets. Each carton contains one bottle.
Lazcluze 240 mg film-coated tablets:
Blister pack:
Polyvinyl chloride – polychlorotrifluoroethylene (PVC-PCTFE) film and aluminium push-through foil.
Bottle:
White opaque high-density polyethylene (HDPE) bottle with polypropylene child-resistant closure containing 30 film-coated tablets. Each carton contains one bottle.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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