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LAZCLUZE®

(lazertinib)

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LAZCLUZE® (lazertinib)
Medical Information

LAZCLUZE - Safety Information for LAZCLUZE - Hepatotoxicity

Last Updated: 05/12/2026

SUMMARY

  • LAZCLUZE (lazertinib) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI).1
  • RYBREVANT (amivantamab-vmjw) is a low fucose, fully human immunoglobulin G1 (IgG1)-based bispecific antibody with immune cell-directing activity that targets EGFR mutations and mesenchymal-epithelial transition (MET) mutations and amplifications in non-small cell lung cancer (NSCLC).2
  • MARIPOSA (NCT04487080) is an ongoing, phase 3, randomized study evaluating the efficacy and safety of RYBREVANT plus LAZCLUZE (open-label, n=429) vs osimertinib (double-blind, n=429) vs LAZCLUZE (double-blind, n=216) as first-line treatment in patients with EGFR-mutated (Exon 19 deletion [Exon19del] or Exon 21 L858R substitution) locally advanced or metastatic NSCLC.1,3-5
    • Among patients treated with RYBREVANT plus LAZCLUZE, hepatotoxicity occurred in 48.69% of patients, including grade 3-4 hepatotoxicity in 9.74% of patients.6
    • The incidence of hepatotoxicity leading to drug interruption, dose reduction, and drug discontinuation of LAZCLUZE was reported in 8.31%, 1.43%, and 0.24% of patients, respectively.7-9
  • Please refer to LAZCLUZE product labeling for complete safety information, including dose modification guidelines for adverse reactions.

PRODUCT LABELING

CLINICAL DATA

MARIPOSA Study

Study Design/Methods

  • Phase 3, ongoing, randomized study designed to assess the efficacy and safety of RYBREVANT plus LAZCLUZE (open-label, n=429) vs osimertinib (double-blind, n=429) vs LAZCLUZE (double-blind, n=216) as first-line treatment in 1074 patients with EGFRmutated (Exon19del or L858R) locally advanced or metastatic NSCLC.1,3-5
    • RYBREVANT 1050 mg intravenous (IV; 1400 mg IV for body weight ≥80 kg) was administered every week for the first 4 weeks, with the initial dose as a split infusion on cycle 1 day 1 (C1D1) and D2, followed by every 2 weeks thereafter.
    • LAZCLUZE 240 mg was administered orally (PO) once daily.
    • Osimertinib 80 mg PO was administered once daily.
  • As part of inclusion criteria for enrollment, patients had to have adequate hepatic function (alanine aminotransferase [ALT] and aspartate aminotransferase [AST] ≤3 × upper limit of normal [ULN], and total bilirubin ≤1.5 × ULN) without history of red blood cell transfusion, platelet transfusion, or granulocyte colony-stimulating factor within 7 days prior to the date of the test.10
    • Patients with Gilbert’s syndrome were eligible provided conjugated bilirubin was within normal limits.
  • Liver function tests (including ALT, AST, and total bilirubin) were performed before initiation of LAZCLUZE and during treatment, as clinically indicated.11
    • In the MARIPOSA study, chemistry samples for patients treated with RYBREVANT plus LAZCLUZE were collected at screening and at treatment visits (C1D1, C1D8, C1D15, C1D22, C2D1, C2D15, and D1 for C3+), as well as at the end‑of‑treatment visit (within 30 days after the last dose of study treatment).10
    • Assessments performed within 72 hours prior to the first dose of study treatment did not require repeat collection on C1D1.10

Results


MARIPOSA: Incidence of Treatment-Emergent Hepatotoxicity6,12
TEAEs,a n (%)
RYBREVANT + LAZCLUZE
(n=421)
Osimertinib
(n=428)
All Grades
Grade 1-2
Grade 3-4
All Grades
Grade 1-2
Grade 3-4
Hepatotoxicityb
205 (48.69)
164 (38.95)
41 (9.74)
106 (24.77)
87 (20.33)
19 (4.44)
ALT increased
160 (38)
137 (32.54)
23 (5.46)
58 (13.55)
50 (11.68)
8 (1.87)
AST increased
128 (30.4)
114 (27.08)
14 (3.33)
58 (13.55)
53 (12.38)
5 (1.17)
GGT increased
66 (15.68)
53 (12.59)
13 (3.09)
32 (7.48)
26 (6.07)
6 (1.4)
Blood ALP increased
52 (12.35)
47 (11.16)
5 (1.19)
23 (5.37)
21 (4.91)
2 (0.47)
Hyperbilirubinemia
31 (7.36)
30 (7.13)
1 (0.24)
15 (3.5)
15 (3.5)
0
Hepatic function abnormal 
4 (0.95)
3 (0.71)
1 (0.24)
5 (1.17)
3 (0.7)
2 (0.47)
Hepatitis 
4 (0.95)
4 (0.95)
0
0
0
0
Hepatic cytolysis 
2 (0.48)
2 (0.48)
0
1 (0.23)
1 (0.23)
0
Hepatotoxicity 
2 (0.48)
2 (0.48)
0
2 (0.47)
2 (0.47)
0
Hypertransaminasemia 
2 (0.48)
2 (0.48)
0
2 (0.47)
1 (0.23)
1 (0.23)
Liver injury 
2 (0.48)
1 (0.24)
1 (0.24)
0
0
0
Blood bilirubin increased 
1 (0.24)
1 (0.24)
0
1 (0.23)
0
1 (0.23)
Hepatic enzyme increased 
1 (0.24)
1 (0.24)
0
0
0
0
Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyl transferase; MedDRA, Medical Dictionary for Regulatory Activities; TEAE, treatment-emergent adverse event.
aAdverse events are coded using MedDRA v25.0.
bPreferred terms are displayed as adverse event groupings.
Note: Patients are counted only once per event, regardless of frequency of that event.

MARIPOSA: LAZCLUZE Dosage Modifications Due to Hepatotoxicitya,7-9
Hepatotoxicityb Leading to, n (%)
RYBREVANT + LAZCLUZE
(n=421)
All Grades
Grade 1-2
Grade 3-4
LAZCLUZE drug interruption
35 (8.31)
11 (2.61)
24 (5.7)
LAZCLUZE dose reduction
6 (1.43)
4 (0.95)
2 (0.48)
LAZCLUZE drug discontinuation
1 (0.24)
1 (0.24)
0
Abbreviation: MedDRA, Medical Dictionary for Regulatory Activities.
aAdverse events are coded using MedDRA v25.0.
bPreferred terms are displayed as adverse event groupings.
Note: Patients are counted only once per event, regardless of frequency of that event.

Management of Hepatotoxicity

  • Withhold, reduce the dose, or permanently discontinue LAZCLUZE and RYBREVANT based on severity.11
  • For grade 3-4 hepatotoxicity11:
    • Withhold LAZCLUZE and RYBREVANT until the adverse reaction resolves to grade ≤1 or baseline.
    • Resume both drugs at a reduced dose or LAZCLUZE alone.
    • Consider permanently discontinuing LAZCLUZE and RYBREVANT if recovery does not occur within 4 weeks.

Literature Search

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and DerwentDrug File (and/or other resources, including internal/external databases) was conducted on
05 May 2026. The information included in this response is limited to relevant data from the MARIPOSA study.

 

References

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1 Cho BC, Felip E, Hayashi H, et al. MARIPOSA: phase 3 study of first-line amivantamab + lazertinib versus osimertinib in EGFR-mutant non-small-cell lung cancer. Future Oncol. 2022;18(6):639-647.  
2 Moores SL, Chiu ML, Bushey BS, et al. A novel bispecific antibody targeting EGFR and cMet is effective against EGFR inhibitor-resistant lung tumors. Cancer Res. 2016;76(13):3942-3953.  
3 Janssen Research & Development, LLC. A phase 3, randomized study of amivantamab and lazertinib combination therapy versus osimertinib versus lazertinib as first-line treatment in patients with EGFR-mutated locally advanced or metastatic non-small cell lung cancer. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2026 May 05]. Available from: https://clinicaltrials.gov/study/NCT04487080 NLM Identifier: NCT04487080.  
4 Cho BC, Lu S, Felip E, et al. Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC. N Engl J Med. 2024;391(16):1486-1498.  
5 Yang JCH, Lu S, Hayashi H, et al. Overall survival with amivantamab-lazertinib in EGFR-mutated advanced NSCLC. N Engl J Med. 2025;393(17):1681-1693.  
6 Data on File. Lazertinib. Table TSFADR01LAZAHEP1: Incidence of treatment-emergent adverse drug reactions (ADRs) of hepatoxicity for lazertinib by system organ class, preferred term, and toxicity grade (Study 73841937NSC3003). Janssen Research & Development, LLC; 2026.  
7 Data on File. Lazertinib. Table TSFADR01LAZAHEP4: Incidence of treatment-emergent adverse drug reactions (ADRs) of hepatotoxicity leading to lazertinib drug interruption by system organ class, preferred term, and toxicity grade (Study 73841937NSC3003). Janssen Research & Development, LLC; 2026.  
8 Data on File. Lazertinib. Table TSFADR01LAZAHEP5: Incidence of treatment-emergent adverse drug reactions (ADRs) of hepatotoxicity leading to lazertinib dose reduction by system organ class, preferred term, and toxicity grade (Study 73841937NSC3003). Janssen Research & Development, LLC; 2026.  
9 Data on File. Lazertinib. Table TSFADR01LAZAHEP6: Incidence of treatment-emergent adverse drug reactions (ADRs) of hepatotoxicity leading to lazertinib drug discontinuation by system organ class, preferred term, and toxicity grade (Study 73841937NSC3003). Janssen Research & Development, LLC; 2026.  
10 Yang JCH, Lu S, Hayashi H, et al. Protocol for: Overall survival with amivantamab-lazertinib in EGFR-mutated advanced NSCLC. N Engl J Med. 2025;393(17):1681-1693.  
11 LAZCLUZE (lazertinib) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/LAZCLUZE-pi.pdf
12 Data on File. Lazertinib. Table TSFADR01LAZAHEP3: Incidence of treatment-emergent adverse drug reactions (ADRs) of hepatoxicity for lazertinib by system organ class, preferred term, and toxicity grade (Study 73841937NSC3003). Janssen Research & Development, LLC; 2026.