Progression-Free Survival

For first-line treatment of adult patients with locally advanced or metastatic EGFR+ NSCLC

Superior PFS vs osimertinib with a chemo-free combination1

RYBREVANT® + LAZCLUZE™ demonstrated a statistically significant reduction in the risk of progression or death by 30% vs osimertinib1,2

Mariposa trial reduced progression rates for RYBREVANT® (amivantamab) and LAZCLUZE™ patientsRYBREVANT® (amivantamab) and LAZCLUZE™ progression-free rates in the Mariposa trial

7.1-month improvement in mPFS vs osimertinib1

  • 23.7 months (95% CI: 19.1, 27.7) mPFS with RYBREVANT® + LAZCLUZE™ vs 16.6 months (95% CI: 14.8, 18.5) with osimertinib

  • In the non-registrational LAZCLUZE™ arm, mPFS was 18.5 months (95% CI: 14.8, 20.1)2
MARIPOSA study design

NCCN CATEGORY 1 FIRST-LINE THERAPY3*

First-line amivantamab-vmjw (RYBREVANT®) + lazertinib (LAZCLUZE™) is an NCCN Category 1 recommended treatment option for patients with EGFR+† mNSCLC.‡§

*EGFR mutation discovered prior to first-line systemic therapy.3

†EGFR exon 19 deletion or exon 21 L858R mutations.3

‡See the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for detailed recommendations, including other treatment options.3

§Prophylactic anticoagulation is recommended at the time of initiation to prevent venous thromboembolic events.3

PFS results in prespecified subgroups2

Mariposa trial disease progression rates for RYBREVANT® and LAZCLUZE™Mariposa trial disease progression rates for RYBREVANT® and LAZCLUZE™Mariposa trial disease progression rates for RYBREVANT® and LAZCLUZE™

High-risk features at baseline were identified in 89% of patients with baseline ctDNA available for NGS of pathogenic alterations (N=636)2,4

This analysis is not included in the Prescribing Information for RYBREVANT® and LAZCLUZE™. This was a post hoc exploratory analysis and was not powered to show statistical significance.
*In MARIPOSA, pathogenic alterations were identified by NGS using ctDNA from blood with Guardant360 CDx at baseline. Ex19del and L858R ctDNA in blood was analyzed at baseline with Biodesix ddPCR. This exploratory analysis included all randomized patients who had 1 or more biomarker assessments. Subgroup analyses of efficacy endpoints were carried out using statistical methods for the primary analysis of the general MARIPOSA population.
†Consistent results were seen in patients with detectable ctDNA using NGS (HR: 0.71 [95% CI: 0.57, 0.89]).

CI, confidence interval; ctDNA, circulating tumor DNA; ddPCR, droplet digital polymerase chain reaction; DNA, deoxyribonucleic acid; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; ex19del, exon 19 deletion; HR, hazard ratio; mPFS, median progression-free survival; NCCN, National Comprehensive Cancer Network; NE, not estimable; NGS, next-generation sequencing; NSCLC, non–small cell lung cancer; PFS, progression-free survival; TP53, tumor protein p53.

Overall Survival

For first-line treatment of adult patients with locally advanced or metastatic EGFR+ NSCLC

The first and only regimen to achieve statistically significant overall survival improvement vs osimertinib5

RYBREVANT® + LAZCLUZE™ reduced the risk of death by 25% vs osimertinib (P<0.005)

RYBREVANT® (amivantamab) with carboplatin and pemetrexed dosing and administration breakdown over timeRYBREVANT® (amivantamab) and LAZCLUZE™ survival rates in Mariposa trial

Median OS was not reached (95% CI: 42.9, NR) with RYBREVANT® + LAZCLUZE™ vs 36.7 months (95% CI: 33.4, 41) with osimertinib5
  • At 3.5 years, 56% of patients were alive with RYBREVANT® + LAZCLUZE™ vs 44% with osimertinib5

NR, not reached; OS, overall survival.

Other Endpoints

For first-line treatment of adult patients with locally advanced or metastatic EGFR+ NSCLC

High and durable responses with a chemo-free combination1

Overall response rate1

  • ORR was 78% (95% CI: 74, 82) with RYBREVANT® + LAZCLUZE™ (N=429) and 73% (95% CI: 69, 78) with osimertinib (N=429)
  • 73% of patients treated with RYBREVANT® + LAZCLUZE™ achieved a PR and 70% of patients treated with osimertinib
  • 5.4% of patients treated with RYBREVANT® + LAZCLUZE™ achieved a CR and 3.5% of patients treated with osimertinib

This was a prespecified analysis and was not powered to show statistical significance.

Duration of response1

Median duration of response

RYBREVANT® (amivantamab) and LAZCLUZE™ median duration of response bar chartRYBREVANT® (amivantamab) and LAZCLUZE™ median duration of response

This was a prespecified analysis and was not powered to show statistical significance.

~1.5X mDOR with RYBREVANT® + LAZCLUZE™1

For the treatment of adult patients with locally advanced or metastatic EGFR+ NSCLC

Intracranial PFS5*

Intracranial PFS at 36 months in subjects with intracranial lesions at baseline

RYBREVANT® (amivantamab) patients in Mariposa trial maintaining intracranial response bar graphIntracranial response in RYBREVANT® and LAZCLUZE™ bar graph

This was a prespecified secondary analysis and was not powered to show statistical significance.

Intracranial PFS at 36 months was 36% with RYBREVANT® + LAZCLUZE™ and 18% with osimertinib5

For first-line treatment of adult patients with locally advanced or metastatic EGFR+ NSCLC

High intracranial ORR with durable intracranial DOR5,6

Intracranial ORR in subjects with intracranial lesions at baseline*

  • Intracranial ORR was 78% (95% CI: 71, 84) with RYBREVANT® + LAZCLUZE™ (N=180) and 77% (95% CI: 71, 83) with osimertinib (N=186)

This was a prespecified exploratory analysis and was not powered to show statistical significance.

Intracranial DOR in subjects with intracranial lesions at baseline*

Median intracranial duration of response

RYBREVANT® (amivantamab) patients in Mariposa trial maintaining intracranial response bar graphIntracranial response in RYBREVANT® and LAZCLUZE™ bar graph

This was a prespecified exploratory analysis and was not powered to show statistical significance.

Median intracranial DOR was 35.7 months (95% CI: 25.8, NR) with RYBREVANT® + LAZCLUZE™ and 29.6 months (95% CI: 23.9, 34.1) with osimertinib5

*Based on median follow-up of 37.8 months.5

CR, complete response; DOR, duration of response; mDOR, median duration of response; ORR, overall response rate; PR, partial response.

Study Design

For first-line treatment of adult patients with locally advanced or metastatic EGFR+ NSCLC

MARIPOSA: Evaluating the first and only multitargeted combination in first-line EGFR+ mNSCLC vs osimertinib1

MARIPOSA was a randomized, active-controlled, multicenter Phase 3 trial assessing the efficacy of RYBREVANT® in combination with LAZCLUZE™. Eligible patients were required to have untreated locally advanced or metastatic NSCLC with either EGFR exon 19 deletions or exon 21 L858R substitution mutations identified by local testing, not amenable to curative therapy. Patients with asymptomatic or previously treated and stable intracranial metastases were eligible to enroll. Patients were randomized (2:2:1) to receive RYBREVANT® in combination with LAZCLUZE™ (n=429), osimertinib monotherapy (n=429), or LAZCLUZE™ monotherapy (an unapproved regimen for NSCLC) until disease progression or unacceptable toxicity. The evaluation of efficacy for the treatment of untreated metastatic NSCLC relied upon comparison between RYBREVANT® in combination with LAZCLUZE™, and osimertinib.1,2

Serial brain MRIs were conducted for all patients to assess intracranial response and duration2

  • Serial brain MRIs were performed at baseline and either every 8 weeks for the first 30 months and 12 weeks thereafter (for patients with a history of brain metastases) or every 24 weeks (for patients without a history)

The largest Phase 3 trial of patients with EGFR+ disease2,8-18*

Mariposa trial study design for RYBREVANT® and LAZCLUZE™Mariposa study design for RYBREVANT® and LAZCLUZE™

  LAZCLUZE™ monotherapy arm was included to assess the contribution of the components.2

*MARIPOSA was the largest Phase 3 trial that evaluated 1L treatment in patients with EGFR+ mNSCLC as of April 2025.2,8-18

Baseline characteristics were well-balanced across treatment types2

RYBREVANT® (amivantamab) and LAZCLUZE™ Mariposa trial study design characteristics chartMariposa trial study design baseline characteristics

*Other includes American Indian or Alaska Native, Black or African American, Native Hawaiian or Pacific Islander, multiple, and unknown.

†One patient in the RYBREVANT® + LAZCLUZE™ arm had both ex19del and L858R.

1L, first-line; BICR, blinded independent central review; mNSCLC, metastatic non–small cell lung cancer; MRI, magnetic resonance imaging; RECIST, Response Evaluation Criteria in Solid Tumors.

Safety

Safety profile of RYBREVANT® + LAZCLUZE™ in the MARIPOSA trial1

Majority of ARs were Grades 1 and 2

ARs (≥10%) in patients in MARIPOSA

RYBREVANT® (amivantamab) and LAZCLUZE™ adverse reactions in Mariposa trialRYBREVANT® (amivantamab) and LAZCLUZE™ adverse reactions in Mariposa trial

*Grouped terms.

†Applicable for RYBREVANT® only.

  • Serious ARs occurred in 49% of patients with RYBREVANT® + LAZCLUZE™ and 33% with osimertinib1,2
  • Serious ARs in ≥2% of patients included VTE (11%), pneumonia (4%), rash (2.9%), ILD/pneumonitis (2.9%), COVID-19 (2.4%), pleural effusion (2.1%), and IRR (2.1%)1
  • Fatal ARs occurred in 7% of patients who received RYBREVANT® + LAZCLUZE™ and 7% with osimertinib1,2
  • The most common ARs (≥20%) were rash, nail toxicity, IRR, edema, musculoskeletal pain, stomatitis, VTE, paresthesia, fatigue, diarrhea, constipation, COVID-19, dry skin, hemorrhage, decreased appetite, pruritus, nausea, and ocular toxicity1
  • Clinically relevant ARs in <10% of patients who received RYBREVANT® + LAZCLUZE™ included ILD/pneumonitis (3.1%)1

Select laboratory abnormalities that worsened from baseline (≥20%) in MARIPOSA1*

Lab abnormalities observed with RYBREVANT® (amivantamab) and LAZCLUZE™ in Mariposa trialLab abnormalities observed with RYBREVANT® (amivantamab) and LAZCLUZE™ in Mariposa trial

*The denominator used to calculate the rate is the number of patients with a baseline value and at least one post-treatment value for the specific lab test.

The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased albumin, decreased sodium, increased ALT, decreased potassium, decreased hemoglobin, increased AST, increased GGT, and increased magnesium.1

Key ARs occurred most frequently during the first 4 months and declined over the next 4 months6*

RYBREVANT® and LAZCLUZE™ adverse reactions observed in Mariposa trialRYBREVANT® and LAZCLUZE™ adverse reactions observed in Mariposa trial

This analysis is not included in the Prescribing Information for RYBREVANT® + LAZCLUZE™. This was a post hoc exploratory analysis.

*Patients with PFS events or censored in the first 4 months were excluded from this analysis.

Mariposa trial IRR per RYBREVANT® infusion chartIRRs per RYBREVANT® infusion in Mariposa trial
  • 92.3% of IRRs were Grades 1 to 2
  • Median time to onset of first IRR was 1 hour (range, 0.05 to 52.5 hours)
  • Monitor patients for any signs and symptoms of IRRs during RYBREVANT® infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT® based on severity1
  • If an anaphylactic reaction occurs, permanently discontinue RYBREVANT®1
  • Signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting1

ALT, alanine aminotransferase; AR, adverse reaction; AST, aspartate aminotransferase; GGT, gamma-glutamyl transferase; ILD, interstitial lung disease; IRR, infusion-related reaction; VTE, venous thromboembolism.

Discontinuation Rates and Dose Modifications

90% of patients treated with RYBREVANT® + LAZCLUZE™ were able to stay on treatment without discontinuation due to treatment-related ARs2

Discontinuation Rates

  • Median duration of treatment was 18.5 months for RYBREVANT® + LAZCLUZE™ and 18 months for osimertinib2
  • Permanent discontinuation of RYBREVANT® due to an AR occurred in 34% of patients. ARs leading to RYBREVANT® discontinuation in ≥1% of patients included rash, IRRs, nail toxicity, VTE, ILD/pneumonitis, pneumonia, edema, hypoalbuminemia, fatigue, paresthesia, and dyspnea1
  • Permanent discontinuation of LAZCLUZE™ due to an AR occurred in 21% of patients. ARs that resulted in permanent discontinuation of LAZCLUZE™ in ≥1% of patients included ILD/pneumonitis, pneumonia, VTE, rash, respiratory failure, and sudden death19

Dose Interruptions

  • Dose interruptions of RYBREVANT® due to an AR occurred in 88% of patients. ARs requiring dose interruption in ≥5% of patients were IRRs, rash, nail toxicity, COVID-19, VTE, increased ALT, edema, and hypoalbuminemia1
  • Dose interruptions of LAZCLUZE™ due to an AR occurred in 72% of patients. ARs requiring dose interruption in ≥5% of patients were rash, nail toxicity, COVID-19, VTE, increased ALT, and increased AST19

Dose Reductions

  • Dose reductions of RYBREVANT® due to an AR occurred in 46% of patients. ARs requiring dose reductions in ≥5% of patients were rash and nail toxicity1
  • Dose reductions of LAZCLUZE™ due to an AR occurred in 42% of patients. ARs requiring dose reductions in ≥5% of patients were rash and nail toxicity19

The rate of discontinuations of all agents due to treatment-related ARs was 10% for RYBREVANT® + LAZCLUZE™2

Association of dose interruptions with PFS20*†

Median PFS after 4 months was similar between patients with and without dose interruptions.

  • In this analysis, dose interruption is defined as a skipped dose that is not made up; this population may also include patients that had a dose reduction or drug discontinuation

This analysis is not included in the Prescribing Information for RYBREVANT® + LAZCLUZE™. This was post hoc exploratory analysis.

*In this descriptive analysis of PFS, the hazard ratio by multivariable analysis (via multivariate Cox proportional hazards model, only included patients still at risk of PFS at 4 months) adjusted for age, ECOG PS, EGFR mutation type, Asian race, and history of brain metastases was 1.06 (95% CI: 0.73, 1.44).

†To minimize bias, outcomes (such as progression events or deaths that could occur before interruptions leading to outcomes-based selection bias) were evaluated after the first 4 months. Patients who discontinued study, had disease progression, or died in the first 4 months were not evaluated, as they were not in the study by the cutoff timepoint (and the outcome event may have occurred prior to the interruption).

See Proactive Therapy Management to help reduce the risk of key ARs

Learn more

2L, second-line.

References:

  1. RYBREVANT® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
  2. Cho BC, Lu S, Felip E, et al; MARIPOSA Investigators. Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC. N Engl J Med. 2024;391(16):1486-1498.
  3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed January 16, 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  4. Felip E, Cho BC, Alip A, et al. Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA. Ann Oncol. 2024;35(9):805-816.
  5. Yang JC-H, Kim YJ, Lee S-H, et al. Amivantamab plus lazertinib vs osimertinib in first-line EGFR-mutant advanced NSCLC: Final overall survival from MARIPOSA. Presented at: European Lung Cancer Congress 2025; March 26-29, 2025; Paris, France.
  6. Data on file. Janssen Biotech, Inc.
  7. Cho BC, Lu S, Felip E, et al; MARIPOSA Investigators. Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC. Supplementary Appendix. N Engl J Med. 2024;391(16):1486-1498.
  8. Yang JCH, Wu YL, Schuler M, et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015;16(2):141-151.
  9. Wu YL, Cheng Y, Zhou X, et al. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18:1454-1466. doi:10.1016/S1470-2045(17)30608-3
  10. Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13:239-246. doi:10.1016/S1470-2045(11)70393-X
  11. Nacagawa K, Garon EB, Seto T, et al. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(12):1655-1669.
  12. Kawashima Y, Fukuhara T, Saito H, et al. Bevacizumab plus erlotinib versus erlotinib alone in Japanese patients with advanced, metastatic, EGFR-mutant non-small-cell lung cancer (NEJ026): overall survival analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Respir Med. 2022;10(1):72-82.
  13. Douillard JY, Ostoros G, Cobo M, et al. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br J Cancer. 2014;110(1):55-62.
  14. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin–paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947-957.
  15. Soria JC, Ohe Y, Vansteenkiste J, et al; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non–small-cell lung cancer. N Engl J Med. 2018;378(2):113-125.
  16. Planchard D, Jänne PA, Cheng Y, et al; FLAURA2 Investigators. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948.
  17. Mok TS, Wu YL, Ahn MJ, et al. Osimertinib or platinum–pemetrexed in EGFR T790M–positive lung cancer. N Engl J Med. 2017;376(7):629-640.
  18. Goldberg SB, Pulla MP, Lisberg AE, et al. 123TiP: TROPION-Lung14: A phase III study of osimertinib ± datopotamab deruxtecan (Dato-DXd) as first-line (1L) treatment for patients with EGFR-mutated locally advanced or metastatic (LA/M) non-small cell lung cancer (NSCLC). J Thorac Oncol. 2025;20(suppl 1):S86-S87.
  19. LAZCLUZE™ [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
  20. Campelo MRG, Cho BC, Girard N, et al. Effect of amivantamab dose interruptions on efficacy and safety of first-line amivantamab plus lazertinib in EGFR-mutant advanced NSCLC: exploratory analyses from the MARIPOSA study. Presented at: European Lung Cancer Congress 2024; March 20-23, 2024; Prague, Czech Republic.