SUMMARY

• LAZCLUZE (lazertinib) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI).¹
• No prospective, randomized, head-to-head trials comparing the efficacy and safety of LAZCLUZE with osimertinib have been published.
• MARIPOSA (NCT04487080) is an ongoing, phase 3, randomized study evaluating the efficacy and safety of RYBREVANT (amivantamab-vmjw) and LAZCLUZE combination therapy (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 non-small cell lung cancer (NSCLC). The primary endpoint (RYBREVANT plus LAZCLUZE vs osimertinib) is progression-free survival (PFS), based on blinded independent central review (BICR).^1-3
  • The study was not designed to evaluate a statistical analysis between the LAZCLUZE and osimertinib arms.
  • LAZCLUZE monotherapy was administered to patients to evaluate the contribution of the components in the combination treatment.³
• A randomized, double-blind, exploratory analysis evaluated the efficacy and safety of single-agent LAZCLUZE (n=216) vs osimertinib (n=429) in patients with EGFR-mutated locally advanced or metastatic NSCLC enrolled in the MARIPOSA study.⁴
  • At a median follow-up of 22 months, median PFS by BICR for LAZCLUZE vs osimertinib was 18.5 months (95% confidence interval [CI], 14.8-20.1) vs 16.6 months (95% CI, 14.8-18.5; hazard ratio [HR], 0.98 [95% CI, 0.79-1.22]; P=0.86).
  • Most treatment-emergent adverse events (TEAEs) were grade 1-2 in severity for LAZCLUZE and osimertinib. Patients receiving LAZCLUZE vs osimertinib reported higher rates of rash (45% vs 31%), muscle spasms (23% vs 7%), and paresthesia (15% vs 6%) but lower rates of diarrhea (32% vs 44%), thrombocytopenia (9% vs 20%), and neutropenia (3% vs 13%).
  • A reduced risk of cardiomyopathy (P=0.056) and lower rates of QT interval prolongation (P=0.005) were observed with LAZCLUZE vs osimertinib.
• A real-world study evaluating the effectiveness of LAZCLUZE vs osimertinib in patients with advanced EGFR T790M-positive NSCLC has been published.⁵

PRODUCT LABELING

• LAZCLUZE (lazertinib) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/LAZCLUZE-pi.pdf.
• RYBREVANT (amivantamab-vmjw) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/RYBREVANT-pi.pdf.

clinical study

MARIPOSA Study

Study Design/Methods^1-3

• Ongoing phase 3, randomized study designed to evaluate the efficacy and safety of RYBREVANT and LAZCLUZE combination therapy (open-label) vs osimertinib (double-blind) vs LAZCLUZE (double-blind) as first-line treatment in patients with EGFR-mutated (Exon19del or Exon 21 L858R substitution) locally advanced or metastatic NSCLC.
• The study design is shown in Figure: MARIPOSA Study Design.
  • The study was not designed to evaluate a statistical analysis between the LAZCLUZE and osimertinib arms.
  • LAZCLUZE monotherapy was administered to patients to evaluate the contribution of the components in the combination treatment.³

MARIPOSA Study: Exploratory Analysis

Study Design/Methods⁴

• A randomized, double-blind, exploratory analysis evaluated the efficacy and safety of single-agent LAZCLUZE (n=216) vs osimertinib (n=429) in patients with EGFR-mutated locally advanced or metastatic NSCLC enrolled in the MARIPOSA study.

Results⁴

Efficacy

• At a median follow-up of 22 months, median PFS by BICR for LAZCLUZE vs osimertinib was
  18.5 months (95% CI, 14.8-20.1) vs 16.6 months (95% CI, 14.8-18.5; HR, 0.98 [95% CI, 0.79-1.22]; P=0.86).
  • The PFS rates for LAZCLUZE vs osimertinib were 52% vs 48% at 18 months and 35% vs 34% at 24 months.
  • PFS across prespecified and high-risk subgroups was evaluated for LAZCLUZE vs osimertinib (Table: PFS Across Prespecified Subgroups and Table: PFS Across High-risk Subgroups, respectively).

• The objective response rate (ORR) by BICR among all responders for LAZCLUZE vs osimertinib was 83% vs 85% (P=0.57). The ORR, best response, and duration of response (DOR) by BICR for LAZCLUZE vs osimertinib are included in Table: ORR, Best Response, and DOR by BICR.

• Median time to symptomatic progression (TTSP; defined as the time from randomization to the first onset of new/worsening of lung cancer symptoms requiring a change in therapy, clinical intervention, or death) for LAZCLUZE vs osimertinib was not estimable (NE) vs 29.3 months (95% CI, 25.3-NE; HR, 0.85 [95% CI, 0.65-1.13]; P=0.27).
• At the interim analysis, median overall survival (OS) for LAZCLUZE vs osimertinib was NE (HR, 1.00 [95% CI, 0.73-1.38]; P=1.00).

Safety

• Most TEAEs were grade 1-2 in severity for LAZCLUZE and osimertinib (Table: Summary of TEAEs).
• Serious adverse events (AEs) were reported in 35% of patients treated with LAZCLUZE and 33% of patients treated with osimertinib.
• AEs leading to death were reported in 6% of patients treated with LAZCLUZE and 7% of patients treated with osimertinib.
• The incidence of interstitial lung disease and pneumonitis was 3% for both LAZCLUZE and osimertinib.
• Higher incidence rates of rash (45% vs 31%), muscle spasms (23% vs 7%), and paresthesia (15% vs 6%) were reported with LAZCLUZE vs osimertinib.
• Lower incidence rates of diarrhea (32% vs 44%), thrombocytopenia (9% vs 20%), and neutropenia (3% vs 13%) were reported with LAZCLUZE vs osimertinib.
• Treatment-related discontinuations were reported in 5% of patients treated with LAZCLUZE and 3% of patients treated with osimertinib.

• A reduced risk of cardiomyopathy (P=0.056) and lower rates of QT interval prolongation (P=0.005) were observed with LAZCLUZE vs osimertinib (Table: Cardiac Safety Profile of LAZCLUZE vs Osimertinib).

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 05 September 2024.