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Data published in The New England Journal of Medicine demonstrate RYBREVANT®▼(amivantamab) plus LAZCLUZE®▼ (lazertinib) could re-set survival expectations in first-line EGFR-mutated advanced lung cancer

07-09-2025

Chemotherapy-free combination regimen has the potential to usher in new era for first-line treatment, with median overall survival projected to exceed four years, surpassing monotherapy TKI osimertinib by more than one year*¹

BEERSE, BELGIUM, Sept. 07, 2025 (GLOBE NEWSWIRE) -- Janssen-Cilag International NV, a Johnson & Johnson company, today announced The New England Journal of Medicine (NEJM) published results from the Phase 3 MARIPOSA study. Head-to-head comparison data versus osimertinib monotherapy showed RYBREVANT^®▼(amivantamab) plus LAZCLUZE^®▼(lazertinib) demonstrated a statistically significant and clinically meaningful overall survival (OS) improvement for patients with previously untreated (first-line) locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations.¹

At a median follow-up of 37.8 months, amivantamab plus lazertinib showed a statistically significant reduction in the risk of death compared to osimertinib monotherapy (hazard ratio [HR], 0.75; 95 percent confidence interval [CI], 0.61-0.92, P=0.005).¹ The median OS for the combination was explored as a secondary endpoint and has not yet been reached (95 percent CI, 42.9-not estimable).¹ Median OS for the combination is projected to exceed over four years (absolute increase of over one year) compared to the median of three years observed with osimertinib monotherapy (36.7 months; 95 percent CI, 33.4-41.0).*¹

“This is a turning point in how we treat EGFR-mutated lung cancer,” said Dr. James Chih-Hsin Yang**, M.D., Ph.D, Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan, and lead author on the NEJM manuscript. “We’re now seeing the potential for patients to live significantly longer than we thought possible. Starting with amivantamab plus lazertinib may prevent common types of resistance and reserves chemotherapy for later lines of therapy, which can help achieve better outcomes.”

Through the triple mode of action which includes targeting EGFR mutations from two angles, blocking MET and engaging the immune system, the amivantamab plus lazertinib regimen has the potential to change the natural course of the disease by reducing the spectrum and complexity of acquired resistance mechanisms.²^,3,4,5

“These results reflect years of dedicated research and mark a pivotal step that redefines the treatment of EGFR-mutated advanced lung cancer,” said Henar Hevia, Ph.D., Senior Director, EMEA Therapy Area Head, Oncology, Johnson & Johnson Innovative Medicine. “These published data further reinforce the potential of the chemotherapy-free, dual-targeted amivantamab plus lazertinib regimen to deliver meaningful, long-term clinical outcomes and experiences for patients and their families versus the current standard of care, and that’s what drives our commitment to innovation, every day.”

Further analyses in the publication showed that patients treated with amivantamab plus lazertinib went more than six months longer before receiving additional treatment compared to those who received osimertinib monotherapy (median time to subsequent therapy; 30.3 months vs 24.0 months HR, 0.76; 95 percent CI, 0.64-0.90).¹The amivantamab plus lazertinib combination also improved progression-free survival after subsequent therapy (PFS2), with a median of 42.9 months vs 32.8 months for osimertinib monotherapy (HR, 0.74; 95 percent CI, 0.61-0.90).¹ These findings support the sustained clinical benefit of the combination beyond the first-line setting.¹

“With these results, we have the potential to change the trajectory of this disease,” said Joshua Bauml, M.D., Vice President, Disease Area Leader, Lung Cancer, Johnson & Johnson Innovative Medicine. “Unmet needs remain high for people living with EGFR-mutated lung cancer. Now, we’re delivering survival outcomes that have the ability to redefine what first-line treatment can achieve.”

The safety profile of amivantamab plus lazertinib was consistent with the primary analysis, with treatment emergent adverse event (TEAE) rates comparable to other amivantamab regimens.¹ No new safety signals were identified with the additional longer-term follow-up.¹ The most common TEAEs of any grade that occurred were paronychia (69 percent), infusion-related reaction (65 percent) and rash (64 percent).¹ Amivantamab plus lazertinib had higher rates of EGFR- and MET-related TEAEs compared to osimertinib monotherapy, except diarrhoea, for which rates were higher for osimertinib monotherapy.¹ The most common Grade 3 or higher adverse events (AEs) were rash (17 percent), paronychia (12 percent), dermatitis acneiform (9 percent), pulmonary embolism*** (9 percent) and alanine transaminase increase (7 percent).¹ Most key AEs occurred early during amivantamab and lazertinib treatment.¹ Findings from other studies with amivantamab suggest that implementing prophylactic measures from the onset of amivantamab and lazertinib treatment may significantly reduce the risk of skin reactions, infusion-related reactions and venous thromboembolic events.⁶^,7,8,9

Johnson & Johnson presented the overall survival results at the European Lung Cancer Congress (ELCC) 2025 in Paris in March.¹⁰

About the MARIPOSA Study
MARIPOSA (NCT04487080), which enrolled 1,074 patients, is a randomised, Phase 3 study evaluating amivantamab in combination with lazertinib versus osimertinib monotherapy and versus lazertinib alone in first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or exon 21 L858R substitution mutations.¹¹ The primary endpoint of the study is progression-free survival (PFS) (using RECIST v1.1 guidelines^‡) as assessed by BICR.¹¹ Secondary endpoints include overall survival (OS), overall response rate (ORR), duration of response (DOR), second progression-free survival (PFS2) and intracranial PFS.¹¹ The MARIPOSA study met its primary endpoint in October 2023, showing a statistically significant and clinically meaningful improvement in PFS compared to osimertinib monotherapy.¹¹^,¹²

About Amivantamab
Amivantamab is a fully-human EGFR-MET bispecific antibody that acts by targeting tumours with activating and resistance EGFR mutations and MET mutations and amplifications, and by harnessing the immune system.²^,³^,⁴^,¹³

The European Commission (EC) has approved amivantamab in the following indications:¹³

Intravenous amivantamab:

In combination with lazertinib for the first-line treatment of adult patients with advanced NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations.
In combination with carboplatin and pemetrexed for the treatment of adult patients with advanced NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, after failure of prior therapy including an EGFR TKI.
In combination with carboplatin and pemetrexed, for the first-line treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations.
As monotherapy for treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations, after failure of platinum-based therapy.

Subcutaneous amivantamab:

In combination with lazertinib for the first‑line treatment of adult patients with advanced NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations.
As monotherapy for treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations, after failure of platinum‑based therapy.

Subcutaneous (SC) amivantamab is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE^® drug delivery technology.¹⁴

In May 2025, an application was submitted to the European Medicines Agency (EMA) to extend the amivantamab marketing authorisation for additional subcutaneous dosing regimens, including:¹⁵

The use of an every-three-week (Q3W) SC amivantamab dosing regimen in combination with carboplatin and pemetrexed for the treatment of adult patients with advanced NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, after failure of prior therapy including an EGFR TKI, and for the first-line treatment of adult patients with advanced NSCLC with activating EGFR Exon 20 insertion mutations.
An every-four-week (Q4W) SC amivantamab dosing regimen, in combination with lazertinib for the first-line treatment of adult patients with advanced NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, and as monotherapy for treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy.

For a full list of adverse events and information on dosage and administration, contraindications and other precautions when using amivantamab, please refer to the Summary of Product Characteristics.¹³

▼ In line with EU regulations for new medicines, amivantamab is subject to additional monitoring.

About Lazertinib
In 2018, Janssen Biotech, Inc., entered into a license and collaboration agreement with Yuhan Corporation for the development of lazertinib (marketed as LACLAZA in South Korea). Lazertinib is an oral, third-generation, brain-penetrant EGFR tyrosine kinase inhibitor (TKI) that targets both the T790M mutation and activating EGFR mutations whilst having less activity against wild-type EGFR.¹⁶ An analysis of the efficacy and safety of lazertinib from the Phase 3 study LASER301 was published in The Journal of Clinical Oncology in 2023.¹⁶

For a full list of adverse events and information on dosage and administration, contraindications and other precautions when using lazertinib, please refer to the Summary of Product Characteristics.¹⁷

▼ In line with EU regulations for new medicines, lazertinib is subject to additional monitoring.  

About Non-Small Cell Lung Cancer
In Europe, it is estimated that 484,306 people were diagnosed with lung cancer in 2022.¹⁸ NSCLC accounts for 85 percent of all lung cancer cases.¹⁹ Lung cancer is Europe’s biggest cancer killer, with more deaths than breast cancer and prostate cancer combined.¹⁸

The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.¹⁹ Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.¹⁹^,²⁰ EGFR mutations are present in 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients.²¹^,22,23,24 EGFR ex19del or EGFR exon 21 L858R mutations are the most common EGFR mutations.²⁵ The five-year survival rate for patients with advanced NSCLC and EGFR mutations treated with EGFR TKIs is less than 20 percent and between 25-32 percent of patients receiving the current first-line standard of care, osimertinib, do not survive long enough to reach second-line treatment.²⁶^,27,28

About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow and profoundly impact health for humanity.

Learn more at https://innovativemedicine.jnj.com/emea/. Follow us at https://www.linkedin.com/company/jnj-innovative-medicine-emea/. Janssen-Cilag International NV, Janssen Biotech, Inc. and Janssen-Cilag, S.A. are Johnson & Johnson companies.

Cautions Concerning Forward-Looking Statements
This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of amivantamab. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialise, actual results could vary materially from the expectations and projections of Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes in behaviour and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s most recent Annual Report on Form 10-K, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at http://www.sec.gov/, http://www.jnj.com/ or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments.

*Based on an exponential distribution assumption of OS in both arms, the improvement in median OS is projected to exceed 1 year. The factors included in the model were: baseline mutation type, race, baseline brain metastases, age, sex, ECOG PS, and weight at baseline. This is an estimate and final observed results may vary. 

**Dr. James Chih-Hsin Yang, M.D., Ph.D, has served as a consultant to Johnson & Johnson; he has not been paid for any media work.

***VTE, a grouped term including pulmonary embolism, deep vein thrombosis, limb venous thrombosis, venous thrombosis, thrombosis, superficial vein thrombosis, thrombophlebitis, embolism, venous embolism, jugular vein thrombosis, sigmoid sinus thrombosis, axillary vein thrombosis, pulmonary infarction, vena cava thrombosis, central venous catheteristion, portal vein thrombosis, post thrombotic syndrome, pulmonary thrombosis, superior sagittal sinus thrombosis, transverse sinus thrombosis, pelvic venous thrombosis, and superior vena cava syndrome, occurred in 40 percent of participants in the amivantamab-lazertinib group and 11 percent in the osimertinib group; these events can be managed with prophylactic anticoagulation for the first 4 months of treatment and per local guidelines.

^‡RECIST (v1.1) refers to Response Evaluation Criteria in Solid Tumors, which is a standard way to measure how well solid tumours respond to treatment and is based on whether tumours shrink, stay the same or get bigger. 

Source: Johnson & Johnson

¹ Yang, JCH, et al. Overall Survival with Amivantamab-Lazertinib in EGFR-mutant Advanced NSCLC. N Engl J Med. 2025. Available at: Overall Survival with Amivantamab–Lazertinib in EGFR-Mutated Advanced NSCLC | New England Journal of Medicine. Accessed September 2025

² Moores SL, et al. A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor-Resistant Lung Tumors. Cancer Res 2016;76(13)(suppl 27216193):3942-3953.

³ Grugan KD, et al. Fc-mediated activity of EGFR x c-Met bispecific antibody JNJ-61186372 enhanced killing of lung cancer cells. Mabs. 2017;9(1):114-126.

⁴ Yun J, et al. Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR–MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion–Driven NSCLC. Cancer Discov. 2020;10(8):1194-1209.

⁵ Besse B, et al. Mechanisms of Acquired Resistance to First-line Amivantamab Plus Lazertinib Versus Osimertinib in Patients With EGFR-mutant Advanced Non-Small Cell Lung Cancer: An Analysis from the Phase 3 MARIPOSA Study. 2024 European Society For Medical Oncology Congress. August 2024.

⁶ Innovativemedicine.jnj.com. COCOON study meets primary endpoint demonstrating statistically significant and clinically meaningful reduction in dermatologic reactions with easy-to-use prophylactic regimen for patients with EGFR-mutated NSCLC. January 14, 2025. Accessed March 2025.

⁷ Spira AI, et al. Preventing Infusion-Related Reactions With Intravenous Amivantamab-Results From SKIPPirr, a Phase 2 Study: A Brief Report. J Thorac Oncol. 2025 Jan 24:S1556-0864(25)00051-6.

⁸ Leighl N, et al. PALOMA-3 Investigators. Subcutaneous Versus Intravenous Amivantamab, Both in Combination With Lazertinib, in Refractory Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer: Primary Results From the Phase III PALOMA-3 Study. J Clin Oncol. 2024 Oct 20;42(30):3593-3605.

⁹ Girard, et al. Preventing Moderate to Severe Dermatologic Adverse Events in First-line EGFR-mutant Advanced NSCLC Treated with Amivantamab Plus Lazertinib: Early Success of the COCOON Trial. 2025 European Lung Cancer Congress. March 27, 2025.

¹⁰ Yang J, et al. Amivantamab Plus Lazertinib vs Osimertinib in First-line (1L) EGFR-mutant (EGFRm) Advanced NSCLC: Final Overall Survival (OS) from the Phase 3 MARIPOSA Study. 2025 European Lung Cancer Congress. March 26, 2025.

¹¹ Cho BC, et al. Amivantamab Plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC. The New England Journal of Medicine 2024. doi:10.1056/NEJMoa2403614. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa2403614. Accessed August 2025.

¹² Innovativemedicine.jnj.com/EMEA. Landmark Phase 3 MARIPOSA Study Shows RYBREVANT®▼(amivantamab) Plus Lazertinib Resulted in 30 Percent Reduction in Risk of Disease Progression or Death Compared to Osimertinib in Patients with EGFR-Mutated Non-Small Cell Lung Cancer. Available at: https://innovativemedicine.jnj.com/emea/landmark-phase-3-mariposa-study-shows-rybrevantrvamivantamab-plus-lazertinib-resulted-30-percent. Accessed August 2025

¹³ European Medicines Agency. Amivantamab Summary of Product Characteristics. July 2025. Available at: https://www.ema.europa.eu/en/documents/product-information/rybrevant-epar-product-information_en.pdf. Accessed August 2025.

¹⁴ Leighl NB et al. Subcutaneous Versus Intravenous Amivantamab, Both in Combination With Lazertinib, in Refractory Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer: Primary Results From the Phase III PALOMA-3 Study. ASCO Journal of Clinical Oncology. 2024;42(3):3593-3605.

¹⁵ Innovativemedicine.jnj.com/EMEA. Johnson & Johnson submits application to the European Medicines Agency for additional subcutaneous RYBREVANT®▼(amivantamab) dosing regimens to treat patients with EGFR-mutated advanced non-small cell lung cancer. Available at: https://innovativemedicine.jnj.com/emea/newsroom/johnson-johnson-submits-application-to-the-european-medicines-agency-for-additional-subcutaneous-rybrevant-amivantamab-dosing-regimens-to-treat-patients-with-egfr-mutated-advanced-non-small-cell-lung-cancer Accessed August 2025.

¹⁶ Cho, BC, et al. Lazertinib versus gefitinib as first-line treatment in patients with EGFR-mutated advanced non-small-cell lung cancer: Results From LASER301. J Clin Oncol. 2023;41(26):4208-4217.

¹⁷ European Medicines Agency. Lazcluze. July 2025. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/lazcluze. Accessed August 2025.

¹⁸ Global Cancer Observatory. Cancer Today. Available at: https://gco.iarc.who.int/media/globocan/factsheets/populations/908-europe-fact-sheet.pdf. Accessed August 2025.

¹⁹ Zappa C, et al. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res. 2016;5(3):288–300.

²⁰ Wee P & Wang Z. Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways. Cancers. 2017;9(12):52.

²¹ Pennell NA, et al. A phase II trial of adjuvant erlotinib in patients with resected epidermal growth factor receptor-mutant non-small cell lung cancer. J Clin Oncol. 2019;37(2):97-104.

²² Burnett H, et al. Epidemiological and clinical burden of EGFR exon 20 insertion in advanced non-small cell lung cancer: a systematic literature review. Abstract presented at: World Conference on Lung Cancer Annual Meeting (Singapore); January 29, 2021.

²³ Zhang YL, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016;7(48):78985- 78993.

²⁴ Midha A, et al. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity. Am J Cancer Res. 2015;5(9):2892-2911.

²⁵ American Lung Association. EGFR and Lung Cancer. Available at: https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptomsdiagnosis/biomarker-testing/egfr. Accessed August 2025.

²⁶ Lin JJ, et al. Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs. J Thorac Oncol. 2016;11(4):556-65.

²⁷ Nieva J, 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 (NSCLC). Ann Oncol. 2023;34, S774.

²⁸ Girard N, et al. Mortality among EGFR-mutated advanced NSCLC patients after frontline osimertinib treatment: A real-world, US attrition analysis. J Thorac Oncol. 2023;18(4), S51-52.

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September 2025

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CONTACT: Media contact:
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