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RYBREVANT, LAZCLUZE - Projected Overall Survival Benefit in the MARIPOSA Study
Last Updated: 09/18/2026
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.
- 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
| Parametric Model | RYBREVANT + LAZCLUZE Projected Median OS, Months (95% CI) | Projected Benefit in Median OS, Monthsa | AICb | BICb |
|---|---|---|---|---|
| Exponential | 55.3 (51.8-58.8) | 18.6 | 882.6 | 915.1 |
| Weibull | 50.4 (47.5-53.2) | 13.6 | 877.5 | 914 |
| Generalized gamma | 49.5 (46.9-52.2) | 12.8 | 879 | 919.6 |
| Log-logistic | 52.3 (49.1-55.5) | 15.6 | 880.2 | 916.8 |
| Log-normal | 57.7 (53.7-61.8) | 21 | 898.2 | 934.8 |
| Abbreviations: AIC, Akaike Information Criterion; BIC, Bayesian Information Criterion; CI, confidence interval; OS, overall survival. aCompared to a median OS of 36.7 months from the osimertinib arm based on Kaplan-Meier estimate. bLower values indicate a better fit. | ||||
PRODUCT LABELING
- RYBREVANT (amivantamab-vmjw) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/RYBREVANT-pi.pdf.
- LAZCLUZE (lazertinib) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/LAZCLUZE-pi.pdf.
Literature Search
A literature search of MEDLINE®
REFERENCES
1. 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.
2. 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.
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 September 17]. 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. Yang JCH, Lu S, Hayashi H, et al. Supplement to: Overall survival with amivantamab-lazertinib in EGFR-mutated advanced NSCLC. N Eng J Med. 2025;393(17):1681-1693.
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