SUMMARY

• RYBREVANT (amivantamab-vmjw) is a low fucose, fully human immunoglobulin G1 (IgG1)-based bispecific antibody with immune cell-directing activity that targets epidermal growth factor receptor (EGFR) mutations and mesenchymal-epithelial transition (MET) mutations and amplifications in non-small cell lung cancer (NSCLC).¹
• LAZCLUZE (lazertinib) is a third-generation EGFR tyrosine kinase inhibitor (TKI).²
• MARIPOSA (NCT04487080) is an ongoing, phase 3, randomized study evaluating the efficacy and safety of RYBREVANT 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 or Exon 21 L858R) locally advanced or metastatic NSCLC.^2-4 
  • At a median follow-up of 37.8 months (range, 0-48.1; data cutoff: December 04, 2024), median overall survival (OS) was not estimable (NE; 95% confidence interval [CI], 42.9-NE) for RYBREVANT plus LAZCLUZE and 36.7 months (95% CI, 33.4-41) for osimertinib (hazard ratio [HR], 0.75 [95% CI, 0.61-0.92]; P=0.005).⁵ 
  • As the median OS with RYBREVANT plus LAZCLUZE was not reached, a projection of median OS was performed using median OS of the control group (osimertinib) divided by the HR, based on the assumption of an exponential distribution of OS. The survival benefit of RYBREVANT plus LAZCLUZE vs osimertinib was subsequently assessed by the improvement of median survival time.⁶ 
    • Based on the exponential distribution assumption, the median OS with RYBREVANT plus LAZCLUZE was projected to be 48.9 months (calculated by dividing median OS of 36.7 months with osimertinib by an HR of 0.75), resulting in a survival benefit of 12.2 months over osimertinib.
  • This projection was further supported by an exploratory analysis conducted using 5 widely utilized parametric models: exponential, Weibull, generalized gamma, log-normal, and log-logistic. These models were fitted to the patient-level OS data for RYBREVANT plus LAZCLUZE, incorporating stratification factors (mutation type, Asian race, and history of brain metastasis) and baseline characteristics (including age, sex, Eastern Cooperative Oncology Group performance status, and weight) as predictors.⁶
    • Across all 5 models, median OS with RYBREVANT plus LAZCLUZE was consistently estimated to be >49 months, supporting the projected OS benefit of ≥12 months over osimertinib. See Table: Projected Median OS with RYBREVANT plus LAZCLUZE Based on Parametric Models.

PRODUCT LABELING

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

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 15 September 2025.