For US Healthcare Providers

Important Safety Information RYBREVANT® Prescribing Information LAZCLUZE® Prescribing Information

Prescribing Information

RYBREVANT® Prescribing Information LAZCLUZE® Prescribing Information
Medication Guide
KOL Headshot

Deric Savior, MD

System Division Chief, Hematology/Oncology

Main Line Health System

Wynnewood, Pennsylvania

Dr. Savior is a paid consultant for Johnson & Johnson.
Dr. Savior is a paid consultant for Johnson & Johnson.
“My goal is to choose an effective first-line treatment for my patients with EGFR+ metastatic non–small cell lung cancer to help address the challenges associated with treating these patients.

EGFR+, epidermal growth factor receptor-positive; mNSCLC, metastatic non–small cell lung cancer.

Mechanism of Action

Learn more about how RYBREVANT® + LAZCLUZE® works

Arrow Image

Efficacy Data

Explore the results

Arrow Image

Safety Profile

Review the safety data

Arrow Image

Proactive Therapy Management

Learn more about implementing proactive therapy management

Arrow Image
KOL Headshot KOL Headshot

Patients with EGFR+ metastatic non–small cell lung cancer have a high chance of disease progression, with 25% to 40% never reaching second-line therapy. This highlights the need for additional therapeutic options.

Deric Savior, MD

System Division Chief, Hematology/Oncology

Main Line Health System

Wynnewood, Pennsylvania

Dr. Savior is a paid consultant for Johnson & Johnson.

EGFR+

Despite advancements, there are many challenges associated with treating EGFR+ mNSCLC

~95% of patients icon + ~ 25% to 40% of patients icon + <20% of patients survive 5 years icon ~95% of patients icon + ~ 25% to 40% of patients icon + <20% of patients survive 5 years icon

Patient preference is another key factor in treatment decision-making

image representing patient preference is another key factor in treatment decision-making image representing patient preference is another key factor in treatment decision-making

Regardless of treatment administered, patients with high-risk factors may experience poor outcomes, including OS. OS outcomes for patients with ≥1 risk factor in the MARIPOSA study are currently not available; thus, no conclusions can be drawn on RYBREVANT® (amivantamab-vmjw) and LAZCLUZE® (lazertinib) at this time.2,5,7,10

Range includes patients who died or discontinued the assigned therapy without receiving second-line therapy during follow-up.2-4

As demonstrated by Spira et al and Sabari et al, 2 retrospective cohort studies that used real-world electronic health record data from April 2018 to December 2023. Key individual factors associated with shorter real-world survival included: metastases of the liver, bone, and central nervous system; ECOG PS ≥2; age ≥65 years; and mutations of TP53, CDK-4, and EGFR L858R. The data sources reflected real-world clinical practice settings and actual data captured at the site of care, which may mean some data entries were missing or erroneous.5,6

Data come from a cross-sectional online survey of 160 adult patients, 30 care partners, and 150 clinicians conducted between March and May 2023. Survey questions were informed by a targeted literature review, qualitative interviews, and input from a steering committee that included 2 oncology physicians, an oncology nurse practitioner, a patient advocate, patient, and care partner. Descriptive statistics were generated and reported in aggregate. In addition to “extending their lives,” patients ranked “quality of life” and “functional independence” as the next most important treatment attributes.8

Data come from a survey fielded from February to March 2025 of 150 US patients with stage IIIB, IIIC, and IV NSCLC.9

Explore more insights here

CDK-4, cyclin-dependent kinase 4; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; EGFR+, epidermal growth factor receptor-positive; mNSCLC, metastatic non–small cell lung cancer; NSCLC, non–small cell lung cancer; OS, overall survival; TKI, tyrosine kinase inhibitor; TP53, tumor protein p53.

References: 1. Bazhenova L, Minchom A, Viteri S, et al. Comparative clinical outcomes for patients with advanced NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations. Lung Cancer. 2021;162:154-161. doi:10.1016/j.lungcan.2021.10.020 2. Nieva J, Karia PS, Okhuoya P, et al. A real-world (rw) observational study of long-term survival (LTS) and treatment patterns after first-line (1L) osimertinib in patients (pts) with epidermal growth factor receptor (EGFR) mutation-positive (m) advanced non-small cell lung cancer [ESMO abstract 1344P]. Ann Oncol. 2023;34(suppl 2):S774. doi:10.1016/j.annonc.2023.09.2377 3. Lee JY, Mai V, Garcia M, et al. Treatment patterns and outcomes of first-line osimertinib-treated advanced EGFR mutated NSCLC patients: a real-world study. J Thorac Oncol. 2022;17(9)(suppl):S440. doi:10.1016/j.jtho.2022.07.764 4. Girard N, Leighl NB, Ohe Y, et al. Mortality among EGFR-mutated advanced NSCLC patients after starting frontline osimertinib treatment: a real-world, US attrition analysis. J Thorac Oncol. 2023;18(4)(suppl):S51-S52. doi:10.1016/s1556-0864(23)00273-3 5. Spira Al, Ran T, Lin I, et al. Risk factors associated with suboptimal real-world outcomes in patients with EGFR-mutated non-small cell lung cancer treated with front-line recommended therapy. Adv Ther. 2025;42(7):3547-3561. doi:10.1007/s12325-025-03234-3 6. Sabari JK, Yu HA, Mahadevia P, et al. Overall survival after treatment with first-line osimertinib for EGFR-mutant advanced NSCLC in the US. Presented at: the World Conference on Lung Cancer; September 7-10, 2024; San Diego, CA, USA. E-poster. 7. 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. doi:10.1016/j.annonc.2024.05.541 8. Orr LD, Vanderpoel J, Vadagam P, et al. Patient, care partner, and provider voice in treatment decision-making for non-small cell lung cancer. Patient Educ Couns. Published online April 4, 2025. doi:10.1016/j.pec.2025.108776 9. Data on file. Janssen Biotech, Inc. 10. RYBREVANT® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.

KOL Headshot KOL Headshot

RYBREVANT® + LAZCLUZE® is a chemotherapy-free combination for the treatment of adult patients with EGFR+ locally advanced or metastatic non–small cell lung cancer, offering multitargeted inhibition of EGFR and MET along with central nervous system penetration.

Deric Savior, MD

System Division Chief, Hematology/Oncology

Main Line Health System

Wynnewood, Pennsylvania

Dr. Savior is a paid consultant for Johnson & Johnson.

MECHANISM OF ACTION

RYBREVANT® + LAZCLUZE® changes the biology of the disease by reducing acquired MET amplification and secondary EGFR alterations1

MOA image MOA image

RYBREVANT® + LAZCLUZE® is a chemo-free combination that achieves multitargeted inhibition of EGFR and MET with immune cell-directing activity2-5

Trogocytosis is a process in which one cell, in this case a macrophage, physically extracts and ingests cellular material of another cell.6

ADCC involves the release of cytotoxic granules that cause tumor cell death.3,7

Learn more about mechanism of action

3G, third-generation; ADCC, antibody-dependent cellular cytotoxicity; CNS, central nervous system; EGFR, epidermal growth factor receptor; MET, mesenchymal-epithelial transition; TKI, tyrosine kinase inhibitor.

References: 1. Hayashi H, Besse B, Lee S-H, et al. Mechanisms of acquired resistance to first-line amivantamab plus lazertinib vs osimertinib: updated analysis from MARIPOSA. Presented at: World Conference on Lung Cancer; September 6-9, 2025; Barcelona, Spain. 2. RYBREVANT® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc. 3. Cho BC, Simi A, Sabari J, Vijayaraghavan S, Moores S, Spira A. Amivantamab, an epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET) bispecific antibody, designed to enable multiple mechanisms of action and broad clinical applications. Clin Lung Cancer. 2023;24(2):89-97. doi:10.1016/j.cllc.2022.11.004 4. LAZCLUZE® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc. 5. Yun J, Hong MH, Kim S-Y, et al. YH25448, an irreversible EGFR-TKI with potent intracranial activity in EGFR mutant non–small cell lung cancer. Clin Cancer Res. 2019;25(8):2575-2587. doi:10.1158/1078-0432.CCR-18-2906 6. Bettadapur A, Miller HW, Ralston KS. Biting off what can be chewed: trogocytosis in health, infection, and disease. Infect Immun. 2020;88(7):e00930-19. doi:10.1128/IAI.00930-19 7. Grugan KD, Dorn K, Jarantow SW, et al. Fc-mediated activity of EGFR x c-MET bispecific antibody JNJ-61186372 enhanced killing in lung cancer cells. MAbs. 2017;9(1):114-126. doi:10.1080/19420862.2016

MOA icon MOA icon

“The RYBREVANT® + LAZCLUZE® combination targets EGFR and MET in adult patients with locally advanced or metastatic non–small cell lung cancer. I recommend reviewing the mechanism of action of this therapy, as well as efficacy and safety data, when considering treatment options for your appropriate patients.”

“The RYBREVANT® + LAZCLUZE® combination targets EGFR and MET in adult patients with locally advanced...”

Deric Savior, MD

System Division Chief, Hematology/Oncology

Main Line Health System

Wynnewood, Pennsylvania

Deric Savior, MD

System Division Chief, Hematology/Oncology

Main Line Health System

Wynnewood, Pennsylvania

KOL Headshot KOL Headshot

RYBREVANT® + LAZCLUZE® demonstrated risk reduction of progression or death when compared with osimertinib for treatment of adult patients with locally advanced or metastatic non–small cell lung cancer with EGFR exon 19 deletions or exon 21 L858R substitution mutations. This is an important data point for me to consider when choosing a treatment for my appropriate patients.

Deric Savior, MD

System Division Chief, Hematology/Oncology

Main Line Health System

Wynnewood, Pennsylvania

Dr. Savior is a paid consultant for Johnson & Johnson.

MARIPOSA Trial: A Brief Overview

Overall Survival – Secondary Endpoint

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

Unmatched survival: RYBREVANT® + LAZCLUZE® delivers superior overall survival vs osimertinib with proven durability1,2

Patients who are surviving chart Patients who are surviving chart

Median overall survival not reached with RYBREVANT® + LAZCLUZE® and projected to exceed 4 years3

Based on modeling using observed HR and mOS in the osimertinib group, assuming exponential distribution of OS in both arms. The baseline factors were: mutation type, race, brain metastases, age, sex, ECOG PS, and weight. This is a conservative estimate; final results may vary.3

CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; HR, hazard ratio; mNSCLC, metastatic non–small cell lung cancer; mOS, median overall survival; NE, not estimable; NSCLC, non–small cell lung cancer; OS, overall survival.

Progression-Free Survival – Primary Endpoint

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

Superior PFS vs osimertinib with a chemo-free combination1,4

RYBREVANT® + LAZCLUZE® demonstrated a statistically significant reduction in the risk of progression or death by 30% vs osimertinib1,5

Patients who are progression-free chart Patients who are progression-free chart

7.1-month improvement in mPFS vs osimertinib1

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

In the non-registrational LAZCLUZE® arm, mPFS was 18.5 months (95% CI: 14.8, 20.1)5

National Comprehensive Cancer Network® (NCCN®)
PREFERRED FIRST-LINE THERAPY6*

First-line amivantamab-vmjw (RYBREVANT®) + lazertinib (LAZCLUZE®) is the only NCCN Category 1
preferred multitargeted treatment option for patients with EGFR+† mNSCLC.‡§

EGFR mutation discovered prior to first-line systemic therapy.6

EGFR exon 19 deletion or exon 21 L858R mutations.6

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

Prophylactic anticoagulation is recommended at the time of initiation to prevent venous thromboembolic events.6

EGFR, epidermal growth factor receptor; mNSCLC, metastatic non–small cell lung cancer; mPFS, median progression-free survival; NCCN, National Comprehensive Cancer Network; PFS, progression-free 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 combination1,4

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

Median duration of response1

Median duration of response bar chart Median duration of response bar chart

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

~1.5X mDOR with RYBREVANT® + LAZCLUZE®1

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

CNS Data

The National Comprehensive Cancer Network® (NCCN®) recommends

Amivantamab-vmjw (RYBREVANT®)-based regimens*: The only NCCN preferred combination options for brain metastases in patients with EGFR+† mNSCLC1,7‡

Intracranial PFS§ at 36 months in subjects with intracranial lesions at baseline3

intracranial PFS bar chart intracranial PFS bar chart

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

2X intracranial PFS at 36 months with RYBREVANT® + LAZCLUZE®3

Amivantamab-vmjw + lazertinib; amivantamab-vmjw + carboplatin + pemetrexed.

EGFR exon 19 deletion or exon 21 L858R mutations.7

See the current NCCN Guidelines® for detailed recommendations, including other treatment options.

Based on median follow-up of 37.8 months.3

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

High intracranial ORR with durable intracranial DOR3,8

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)3
    • Intracranial CR was 64% with RYBREVANT® + LAZCLUZE® and 59% with osimertinib8
    • Intracranial PR was 14% with RYBREVANT® + LAZCLUZE® and 19% with osimertinib8

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

Intracranial DOR in confirmed responders with intracranial lesions at baseline8*†

Median intracranial duration of response

Median Intracranial DOR in subjects with intracranial lesions at baseline bar chart Median Intracranial DOR in subjects with intracranial lesions at baseline bar chart

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

Based on median follow-up of 37.8 months.3

Based on subgroup of subjects with history of brain metastasis. CR and PR do not have to be confirmed.8

~1.5X intracranial DOR with RYBREVANT® + LAZCLUZE®8

1L, first-line; CNS, central nervous system; DOR, duration of response; icDOR, intracranial DOR.

NCCN PREFERRED THERAPY FOR BRAIN METASTASES1,7

Amivantamab-vmjw (RYBREVANT®)-based regimens* including amivantamab-vmjw (RYBREVANT®) + lazertinib (LAZCLUZE®) are the only NCCN preferred combination treatment options for brain metastases in patients with EGFR+† mNSCLC.‡

Amivantamab-vmjw + lazertinib; amivantamab-vmjw + carboplatin + pemetrexed.

EGFR exon 19 deletion or exon 21 L858R mutations.7

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

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 osimertinib1,4

MARIPOSA was an active-controlled, multicenter, phase 3 trial. Patients with asymptomatic or previously treated and stable intracranial metastases were eligible to enroll. Patients received treatment until disease progression or unacceptable toxicity. The evaluation of efficacy relied upon comparison between RYBREVANT® in combination with LAZCLUZE®, and osimertinib.1,9

The largest phase 3 trial and the only one that required serial brain MRIs for all patients, providing accurate detection of CNS progression in patients with 1L EGFR+ disease5,9-20*

Largest phase 3 trial with serial brain MRIs for all patients, ensuring accurate detection of CNS progression in 1L EGFR+ disease bar chart Largest phase 3 trial with serial brain MRIs for all patients, ensuring accurate detection of CNS progression in 1L EGFR+ disease bar chart

LAZCLUZE® monotherapy arm was included to assess the contribution of the components.5

MARIPOSA was the largest phase 3 trial that evaluated 1L treatment in patients with EGFR+ mNSCLC as of April 2025.5,9-20

Serial brain MRIs were conducted for all patients to assess intracranial progression and response5

  • 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)

BICR, blinded independent central review; ex19del, exon 19 deletion; MRI, magnetic resonance imaging; RECIST, Response Evaluation Criteria in Solid Tumors.

See more of the clinical study results

References: 1. RYBREVANT® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc. 2. 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; March 26-29, 2025; Paris, France. 3. Yang JC-H, Lu S, Hayashi H, et al; for the MARIPOSA Investigators. Overall survival with amivantamab-lazertinib in EGFR-mutated advanced NSCLC. N Engl J Med. Published online September 7, 2025. doi:10.1056/NEJMoa2503001 4. LAZCLUZE® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc. 5. 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. doi:10.1056/NEJMoa2403614 6. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer. V.3.2026. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed December 26, 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. 7. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Central Nervous System Cancers V.3.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed December 18, 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. 8. Data on file. Janssen Biotech, Inc. 9. 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. doi:10.1056/NEJMoa2403614 10. 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. doi:10.1016/S1470-2045(14)71173-8 11. 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(11):1454-1466. doi:10.1016/S1470-2045(17)30608-3 12. 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(3):239-246. doi:10.1016/S1470-2045(11)70393-X 13. Nakagawa 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. doi:10.1016/S1470-2045(19)30634-5 14. 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. doi:10.1016/S2213-2600(21)00166-1 15. 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. doi:10.1038/bjc.2013.721 16. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin–paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947-957. doi:10.1056/NEJMoa0810699 17. 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. doi:10.1056/NEJMoa1713137 18. 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. doi:10.1056/NEJMoa2306434 19. 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. doi:10.1056/NEJMoa1612674 20. 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. doi:10.1015/S1556-0864(25)00319-3

KOL Headshot KOL Headshot

“I value the efficacy and safety data from a phase 3 clinical study when selecting a treatment for my adult patients with EGFR+ locally advanced or metastatic non–small cell lung cancer. I recommend reviewing these data for RYBREVANT® + LAZCLUZE® as a first-line combination treatment option for your appropriate patients.”

“I value the efficacy and safety data from a phase 3 clinical study when selecting a treatment for my adult patients...”

Deric Savior, MD

System Division Chief, Hematology/Oncology

System Division Chief, Hematology/Oncology

Main Line Health System

Wynnewood, Pennsylvania

Main Line Health System

Wynnewood, Pennsylvania

Deric Savior, MD

System Division Chief, Hematology/Oncology

Main Line Health System

Wynnewood, Pennsylvania

KOL Headshot KOL Headshot

The safety data from the MARIPOSA study showed that most of the patients with previously untreated locally advanced or metastatic EGFR+ non–small cell lung cancer experienced Grades 1 and 2 adverse reactions when they received RYBREVANT® + LAZCLUZE®. I recommend reviewing the possible adverse reactions that may occur when prescribing RYBREVANT® + LAZCLUZE® for your appropriate patients.

Deric Savior, MD

System Division Chief, Hematology/Oncology

Main Line Health System

Wynnewood, Pennsylvania

Dr. Savior is a paid consultant for Johnson & Johnson.

Safety profile of RYBREVANT® + LAZCLUZE® in the MARIPOSA trial

Majority of ARs were Grades 1 and 21

ARs (≥10%) in patients in MARIPOSA1

Adverse Reaction table Adverse Reaction table

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, and nausea1
  • Clinically relevant ARs (<10%) in patients who received RYBREVANT® + LAZCLUZE® included skin ulcer (5.2%) and ILD/pneumonitis (3.1%)1,3

Key ARs occurred more frequently during the first 4 months and declined over the next 4 months3*

Key Adverse Reactions during the first 4 months bar chart Key Adverse Reactions during the first 4 months bar chart

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

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

AR, adverse reaction; ILD, interstitial lung disease; IRR, infusion-related reaction; PFS, progression-free survival; VTE, venous thromboembolism.

Dose Modifications and Discontinuation Rates

Adaptable dosing is available to help your patients manage ARs and stay on treatment3*

Most patients used dose modification to continue treatment with RYBREVANT® + LAZCLUZE®1,4

Median duration of treatment including dose modifications5

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

Certain types and severity of ARs require discontinuation after first occurrence.1

Dose interruptions did not compromise results: Median PFS was similar after 4 months, regardless of whether patients had dose interruptions.6†‡

Median PFS after 4 months was similar between patients with and without dose interruptions bar chart Median PFS after 4 months was similar between patients with and without dose interruptions bar chart
  • In this analysis, dose interruption is defined as a skipped dose that is not made up; this population may also include patients who had a dose reduction or drug discontinuation

This was a post hoc exploratory analysis from MARIPOSA and is not included in the Prescribing Information for RYBREVANT® or LAZCLUZE®.

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).6

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 the 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).6

Discontinuation rates

  • The rate of discontinuation of all agents due to treatment-related ARs was 10% for RYBREVANT® + LAZCLUZE®2
  • Permanent discontinuation of RYBREVANT® due to an AR occurred in 34% of patients1
  • Permanent discontinuation of LAZCLUZE® due to an AR occurred in 21% of patients4

Dose modifications1,4

  • Dose interruptions due to an AR occurred in 88% of patients with RYBREVANT® and 72% of patients with LAZCLUZE®
  • Dose reductions due to an AR occurred in 46% of patients with RYBREVANT® and 42% of patients with LAZCLUZE®
Review additional safety data

CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; NE, not estimable.

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. doi:10.1056/NEJMoa2403614 3. Data on file. Janssen Biotech, Inc. 4. LAZCLUZE® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc. 5. Yang JC-H, Lu S, Hayashi H, et al; for the MARIPOSA Investigators. Overall survival with amivantamab–lazertinib in EGFR-mutated advanced NSCLC. N Engl J Med. Published online September 7, 2025. doi:10.1056/NEJMoa2503001 6. 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; March 20-23, 2024; Prague, Czech Republic.

KOL Headshot KOL Headshot

“I encourage my colleagues to assess the potential benefits and risks of prescribing RYBREVANT® and LAZCLUZE® as a first-line combination treatment as they consider the regimen for their adult patients with locally advanced or metastatic EGFR+ non–small cell lung cancer.”

“I encourage my colleagues to assess the potential benefits and risks of prescribing RYBREVANT® and LAZCLUZE® as a first-line...”

Deric Savior, MD

System Division Chief, Hematology/Oncology

System Division Chief, Hematology/Oncology

Main Line Health System

Wynnewood, Pennsylvania

Main Line Health System

Wynnewood, Pennsylvania

Deric Savior, MD

System Division Chief, Hematology/Oncology

Main Line Health System

Wynnewood, Pennsylvania

KOL Headshot KOL Headshot

On-target adverse reactions are expected with treatments such as RYBREVANT® and LAZCLUZE®, which targets EGFR in patients with locally advanced or metastatic non–small cell lung cancer. I always recommend a proactive therapy management plan for my patients to help them start and continue on EGFR-targeting treatment.

Deric Savior, MD

System Division Chief, Hematology/Oncology

Main Line Health System

Wynnewood, Pennsylvania

Dr. Savior is a paid consultant for Johnson & Johnson.

PROACTIVE THERAPY MANAGEMENT

Patients Receiving RYBREVANT® + LAZCLUZE® Need Proactive Therapy Management

Overview

Use proactive therapy management to help optimize outcomes1

Studies incorporating proactive therapy management demonstrated significantly reduced rates of key ARs2,3

Study Designs:

SKIPPirr

SKIPPirr is a phase 2 prospective study that assessed prophylactic strategies to reduce incidence and/or severity of first-dose IRRs with RYBREVANT®, with dexamethasone 8 mg cohort reaching the expansion stage.* The primary endpoint was the incidence of IRR events on Week 1, Day 1.

Limitations of the study include that SKIPPirr was not a comparative study and dexamethasone 8 mg oral cohort sample size was n=40.3,4

COCOON

COCOON is an ongoing phase 2, open-label, randomized study evaluating the effect of enhanced (N=99) versus standard (N=100) dermatologic management strategies in patients treated with RYBREVANT® + LAZCLUZE® in 1L. The primary endpoint is incidence of Grade ≥2 dermatologic ARs of interest in the first 12 weeks after treatment initiation.2

Use proactive therapy management to help optimize outcomes chart Use proactive therapy management to help optimize outcomes chart

This was a Simon 2-stage design. Stage 1 n=6. Stage 2 n=16. Expansion stage n=40. See full presentation for more details.3

Among all COCOON study participants, the VTE incidence was 11% (n=18/170) from 5 to 8 months.2

1L, first-line; AR, adverse reaction; IRR, infusion-related reaction; VTE, venous thromboembolism.

Protocol

Proactive strategies that may help patients start and stay on RYBREVANT® + LAZCLUZE®

Proactive strategies chart Proactive strategies chart

Month=month of treatment with RYBREVANT® + LAZCLUZE®.

Optional for subsequent doses.5

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommendations for cancer-associated VTE disease: anticoagulant options for VTE prophylaxis for ambulatory patients with cancer include DOACs and LMWHs.6‡

Recommendations derived from clinical trials of ambulatory patients with cancer with high thrombosis risk (>18 years, Khorana VTE Risk Score of ≥2, initiating new course of chemotherapy) and are not included in product labeling. Prophylaxis duration should be 6 months or longer if risk persists.6

DOAC, direct oral anticoagulant; IV, intravenous; LMWH, low molecular weight heparin; NCCN, National Comprehensive Cancer Network; SPF, sun protection factor.

See the full Prescribing Information for RYBREVANT® for prophylactic strategies for reducing the risk of dermatologic ARs.

VTE prophylaxis

COCOON is the first trial that required 4 months of prophylactic anticoagulation at treatment initiation, leading to a low incidence of VTE4

COCOON is the first trial that required 4 months of prophylactic anticoagulation at treatment initiation, leading to a low incidence of VTE bar chart COCOON is the first trial that required 4 months of prophylactic anticoagulation at treatment initiation, leading to a low incidence of VTE bar chart

Among all COCOON study participants, the VTE incidence was 11% (n=18/170) from 5 to 8 months.2

Drug-related prophylaxis for VTE5

Prophylactic treatment with an anticoagulation medicine is recommended for the first 4 months of treatment with RYBREVANT® + LAZCLUZE®

  • The use of Vitamin K antagonists is not recommended
  • If there are no signs or symptoms of VTE during the first 4 months of treatment, consider discontinuation of anticoagulant prophylaxis at the discretion of the healthcare provider

NSCLC, non–small cell lung cancer; VTE, venous thromboembolism.

References: 1. Data on file. Janssen Biotech, Inc. 2. Cho BC, Li W, Spira AI, et al. Enhanced versus standard dermatologic management with amivantamab-lazertinib in EGFR-mutated advanced NSCLC: the COCOON global randomized controlled trial. J Thorac Oncol. 2025;20(10):1517-1530. doi:10.1016/j.jtho.2025.07.117 3. Spira AI, Paz-Ares L, Han J-Y, et al. Preventing infusion-related reactions with intravenous amivantamab—results from SKIPPirr, a phase 2 study. J Thorac Oncol. 2025;20(6):809-816. doi:10.1016/j.jtho.2025.01.018 4. Enhanced dermatologic care to reduce rash and paronychia in epidermal growth factor receptor (EGFR)-mutated non small cell lung cancer (NSCLC) treated first-line with amivantamab plus lazertinib (COCOON). ClinicalTrials.gov identifier: NCT06120140. Updated April 29, 2025. Accessed May 27, 2025. https://www.clinicaltrials.gov/study/NCT06120140 5. RYBREVANT® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc. 6. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Cancer-Associated Venous Thromboembolic Disease V.3.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed November 24, 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. 7. Yang R, Wang H, Lieu D, Li W. Incidence and risk factors of VTE in lung cancer: a meta-analysis. Ann Med. 2024;56(1):1-14. doi:10.1080/07853890.2024.2390200

Chess piece image Chess piece image

“I recommend taking a prophylactic supportive care approach when starting RYBREVANT® + LAZCLUZE® for your patients with EGFR+ locally advanced or metastatic non–small cell lung cancer to help mitigate the risk of adverse reactions and promote treatment tolerability.”

“I recommend taking a prophylactic supportive care approach when starting RYBREVANT® +...”

Deric Savior, MD

System Division Chief, Hematology/Oncology

Main Line Health System

Wynnewood, Pennsylvania

Deric Savior, MD

System Division Chief, Hematology/Oncology

Main Line Health System

Wynnewood, Pennsylvania

INDICATION

RYBREVANT® (amivantamab-vmjw) is indicated in combination with LAZCLUZE® (lazertinib) for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Infusion-Related Reactions

RYBREVANT® can cause infusion-related reactions (IRRs) including anaphylaxis; signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting. The median time to IRR onset is approximately 1 hour.

RYBREVANT® with LAZCLUZE®

In MARIPOSA (n=421), IRRs occurred in 63% of patients, including Grade 3 in 5% and Grade 4 in 1% of patients. IRR-related infusion modifications occurred in 54%, dose reduction in 0.7%, and permanent discontinuation of RYBREVANT® in 4.5% of patients.

Premedicate with antihistamines, antipyretics, and glucocorticoids and infuse RYBREVANT® as recommended. Administer RYBREVANT® via a peripheral line on Week 1 and Week 2 to reduce the risk of IRRs. Monitor patients for signs and symptoms of IRRs 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 severity. If an anaphylactic reaction occurs, permanently discontinue RYBREVANT®.

Interstitial Lung Disease/Pneumonitis

RYBREVANT® can cause severe and fatal interstitial lung disease (ILD)/pneumonitis.

RYBREVANT® with LAZCLUZE®

In MARIPOSA, ILD/pneumonitis occurred in 3.1% of patients, including Grade 3 in 1.0% and Grade 4 in 0.2% of patients. There was one fatal case (0.2%) of ILD/pneumonitis and 2.9% of patients permanently discontinued RYBREVANT® and LAZCLUZE® due to ILD/pneumonitis.

Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold both drugs in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.

Venous Thromboembolic Events with Concomitant Use of RYBREVANT® and LAZCLUZE®

RYBREVANT® in combination with LAZCLUZE® can cause serious and fatal venous thromboembolic (VTE) events, including deep vein thrombosis and pulmonary embolism (PE). Most events occurred during the first four months of therapy.

In MARIPOSA, VTEs occurred in 36% of patients including Grade 3 in 10% and Grade 4 in 0.5% of patients. On-study VTEs occurred in 1.2% of patients (n=5) while receiving anticoagulation therapy. There were two fatal cases of VTE (0.5%), 9% of patients had VTE leading to dose interruptions of RYBREVANT®, and 7% of patients had VTE leading to dose interruptions of LAZCLUZE®; 1% of patients had VTE leading to dose reductions of RYBREVANT®, and 0.5% of patients had VTE leading to dose reductions of LAZCLUZE®; 3.1% of patients had VTE leading to permanent discontinuation of RYBREVANT®, and 1.9% of patients had VTE leading to permanent discontinuation of LAZCLUZE®. The median time to onset of VTEs was 84 days (range: 6 to 777).

Administer prophylactic anticoagulation for the first four months of treatment. The use of Vitamin K antagonists is not recommended. Monitor for signs and symptoms of VTE events and treat as medically appropriate.

Withhold RYBREVANT® and LAZCLUZE® based on severity. Once anticoagulant treatment has been initiated, resume RYBREVANT® and LAZCLUZE® at the same dose level at the discretion of the healthcare provider. In the event of VTE recurrence despite therapeutic anticoagulation, permanently discontinue RYBREVANT® and continue treatment with LAZCLUZE® at the same dose level at the discretion of the healthcare provider.

Dermatologic Adverse Reactions

RYBREVANT® can cause severe rash including toxic epidermal necrolysis (TEN), dermatitis acneiform, pruritus, and dry skin.

RYBREVANT® with LAZCLUZE®

In MARIPOSA, rash occurred in 86% of patients, including Grade 3 in 26% of patients. The median time to onset of rash was 14 days (range: 1 to 556 days). Rash leading to dose interruptions occurred in 37% of patients for RYBREVANT® and 30% for LAZCLUZE®, rash leading to dose reductions occurred in 23% of patients for RYBREVANT® and 19% for LAZCLUZE®, and rash leading to permanent discontinuation occurred in 5% of patients for RYBREVANT® and 1.7% for LAZCLUZE®.

When initiating treatment with RYBREVANT®, prophylactic and concomitant medications are recommended to reduce the risk and severity of dermatologic adverse reactions. Instruct patients to limit sun exposure during and for 2 months after treatment. Advise patients to wear protective clothing and use broad spectrum UVA/UVB sunscreen.

If skin reactions develop, administer supportive care including topical corticosteroids and topical and/or oral antibiotics. For Grade 3 reactions, add oral steroids and consider dermatologic consultation. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. For patients receiving RYBREVANT® in combination with LAZCLUZE®, withhold, reduce the dose, or permanently discontinue both drugs on severity.

Ocular Toxicity

RYBREVANT® can cause ocular toxicity including keratitis, blepharitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, eye pruritus, and uveitis.

RYBREVANT® with LAZCLUZE®

In MARIPOSA, ocular toxicity occurred in 16%, including Grade 3 or 4 ocular toxicity in 0.7% of patients. Withhold, reduce the dose, or permanently discontinue RYBREVANT® and continue LAZCLUZE® based on severity.

Promptly refer patients with new or worsening eye symptoms to an ophthalmologist. Withhold, reduce the dose or permanently discontinue RYBREVANT® based on severity.

Embryo-Fetal Toxicity

Based on animal models, RYBREVANT® and LAZCLUZE® can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential of the potential risk to the fetus.

Advise patients of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of RYBREVANT®, and for 3 weeks after the last dose of LAZCLUZE®.

ADVERSE REACTIONS

RYBREVANT® with LAZCLUZE®

In MARIPOSA (n=421), the most common adverse reactions (ARs) (≥20%) were rash (86%), nail toxicity (71%), infusion-related reactions (IRRs) (RYBREVANT®) (63%), musculoskeletal pain (47%), stomatitis (43%), edema (43%), VTE (36%), paresthesia (35%), fatigue (32%), diarrhea (31%), constipation (29%), COVID-19 (26%), hemorrhage (25%), dry skin (25%), decreased appetite (24%), pruritus (24%), and nausea (21%). The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased albumin (8%), decreased sodium (7%), increased ALT (7%), decreased potassium (5%), decreased hemoglobin (3.8%), increased AST (3.8%), increased GGT (2.6%), and increased magnesium (2.6%).

Serious ARs occurred in 49% of patients, with those occurring in ≥2% of patients including VTE (11%), pneumonia (4%), ILD/pneumonitis and rash (2.9% each), COVID-19 (2.4%), and pleural effusion and IRRs (RYBREVANT®) (2.1% each). Fatal ARs occurred in 7% of patients due to death not otherwise specified (1.2%); sepsis and respiratory failure (1% each); pneumonia, myocardial infarction, and sudden death (0.7% each); cerebral infarction, pulmonary embolism (PE), and COVID-19 infection (0.5% each); and ILD/pneumonitis, acute respiratory distress syndrome (ARDS), and cardiopulmonary arrest (0.2% each).

LAZCLUZE® DRUG INTERACTIONS

Avoid concomitant use of LAZCLUZE® with strong and moderate CYP3A4 inducers. Consider an alternate concomitant medication with no potential to induce CYP3A4.

Monitor for adverse reactions associated with a CYP3A4 or BCRP substrate where minimal concentration changes may lead to serious adverse reactions, as recommended in the approved product labeling for the CYP3A4 or BCRP substrate.

Please read full Prescribing Information for RYBREVANT® and LAZCLUZE®.

cp-464671v4