RYBREVANT®▼ (Amivantamab) Plus LAZCLUZE®▼ (Lazertinib) Reduces Acquired Resistance Versus Osimertinib In First-Line EGFR-Mutated Advanced Non-Small Cell Lung Cancer

(MENAFN- GlobeNewsWire - Nasdaq) New data demonstrate amivantamab combination significantly reduces common EGFR and MET resistance mutations seen with EGFR TKIs¹

BEERSE, BELGIUM , Sept. 06, 2025 (GLOBE NEWSWIRE) -- Janssen-Cilag International NV, a Johnson & Johnson company, today announced new analyses from the Phase 3 MARIPOSA study showing that first-line treatment with RYBREVANT^®▼ (amivantamab) plus LAZCLUZE^®▼ (lazertinib) significantly reduces the development of epidermal growth factor receptor (EGFR)- and MET-driven resistance compared with osimertinib monotherapy in patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) with exon 19 deletion (ex19del) or L858R mutations (Poster Abstract PT1.03).¹ These resistance data build on the combination's previously reported overall survival benefit for this chemotherapy-free regimen and underscore its potential to change the biology of the disease by reducing acquired resistance.^1,2 Late-breaking results are being presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC) .

Resistance to EGFR tyrosine kinase inhibitors (TKIs) remains a common and major barrier to long-term disease control.³ This ongoing challenge underscores the need for next-generation strategies that can more effectively prevent the development of resistance mediated by EGFR and MET and extend survival for patients with EGFR-mutated advanced NSCLC.

“We now have a body of evidence that suggests TKI monotherapy is no longer enough for the majority of patients in the first-line treatment of EGFR-mutated lung cancer,” said Professor Sanjay Popat*, FRCP, Ph.D., medical oncologist at the Royal Marsden Hospital and the Institute of Cancer Research in the United Kingdom.“The MARIPOSA results show that combining amivantamab with lazertinib is an important step forward, reducing EGFR- and MET-driven resistance seen with EGFR TKI monotherapy and giving patients a longer, stronger first response.”

Consistent with prior data presented at the European Society for Medical Oncology (ESMO) 2024 Congress, these updated analyses from the MARIPOSA study confirm that patients treated with amivantamab plus lazertinib were less likely to develop the two main types of resistance observed with osimertinib (MET amplification and secondary EGFR mutations) compared to those treated with osimertinib alone.^1,4 MET amplifications occurred in three percent of patients on the combination versus 13 percent on osimertinib monotherapy (P=0.002), and secondary EGFR mutations (such as C797S) were significantly lower for amivantamab plus lazertinib versus osimertinib monotherapy (one percent vs eight percent; P=0.01).¹ Acquired MET amplification led to early discontinuation in 23 percent of patients on osimertinib monotherapy within six months, compared with four percent on amivantamab plus lazertinib.¹ Among patients who stayed on amivantamab for at least six months, rates of acquired resistance were infrequent, with two percent developing MET amplification and no EGFR C797S mutations observed.¹ The analysis also found greater overall genetic diversity of resistance in patients treated with osimertinib monotherapy, particularly among patients with EGFR- and MET-based alterations.¹

“Amivantamab and lazertinib were purposefully combined to proactively address mechanisms of acquired resistance to EGFR TKIs, one of the greatest challenges and barriers to long-term disease control in EGFR-mutated NSCLC,” said Henar Hevia, Ph.D., Senior Director, EMEA Therapy Area Head, Oncology, Johnson & Johnson Innovative Medicine.“These results add to the growing body of evidence for this innovative combination and reflect our dedication and commitment to advancing treatment options that not only help patients stay on therapy longer but also deliver meaningful outcomes in an area of critical need, bringing new hope to patients and their families.”

The safety profile of amivantamab plus lazertinib was consistent with the primary analysis and no new safety signals emerged with longer-term follow-up.² The most common TEAEs of any grade that occurred were paronychia (69 percent), infusion-related reaction (65 percent), and rash (64 percent).² Most key AEs occurred early in treatment.² Other studies with amivantamab suggest that using preemptive or prophylactic measures can help lower the overall number and severity of skin reactions, infusion-related reactions and venous thromboembolic events.^5,6,7,8

“Choosing the first treatment for EGFR-mutated NSCLC is one of the most important decisions. It can influence how the disease progresses over time,” said Joshua Bauml, M.D., Vice President, Lung Cancer Disease Area Leader, Johnson & Johnson Innovative Medicine.“These data show amivantamab plus lazertinib changes the biology of disease by blocking the resistance pathways cancers typically use to overcome treatment. By reducing resistance in the frontline, we can potentially extend survival and keep future treatment options open for patients.”

Amivantamab plus lazertinib was approved by the European Commission in December 2024 for patients with first-line common EGFR-mutated NSCLC based on the Phase 3 MARIPOSA study.⁹

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.¹⁰ The primary endpoint of the study is progression-free survival (PFS) (using RECIST v1.1 guidelines^‡) as assessed by BICR.¹⁰ Secondary endpoints include overall survival (OS), overall response rate (ORR), duration of response (DOR), second progression-free survival (PFS2) and intracranial PFS.¹⁰ The MARIPOSA study met its primary endpoint in October 2023, showing a statistically significant and clinically meaningful improvement in PFS compared to osimertinib monotherapy.^10,11

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.^12,13,14,15

The European Commission (EC) has approved amivantamab in the following indications:¹⁵

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.¹⁶

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.¹⁷

• 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 .¹⁵

▼ 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.¹⁸ An analysis of the efficacy and safety of lazertinib from the Phase 3 study LASER301 was published in The Journal of Clinical Oncology in 2023.¹⁸

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 .¹⁹

▼ 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 2022.²⁰ NSCLC accounts for 85 percent of all lung cancer cases.²¹ Lung cancer is Europe's biggest cancer killer, with more deaths than breast cancer and prostate cancer combined.²⁰

The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.²¹ Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.^21,22 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.^23,24,25,26 EGFR ex19del or EGFR exon 21 L858R mutations are the most common EGFR mutations.²⁷ 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.^28,29,30

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 . Follow us at . 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 or lazertinib. 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 , 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.

© Janssen-Cilag International NV, Inc. 2025. All rights reserved.

*Professor Sanjay Popat, FRCP, Ph.D., has served as a consultant to Johnson & Johnson; he has not been paid for any media work.

^‡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 Hayashi, H, et al. Mechanisms of Acquired Resistance to First-Line Amivantamab Plus Lazertinib Vs Osimertinib: Updated Analysis from MARIPOSA [IASLC abstract PT1.03]. Presented at: IASLC 2025 World Lung Conference on Lung Cancer; September 6-9, 2025; Barcelona, Spain.

² 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.

³ Tan CS, Kumarakulasinghe NB, Huang YQ, et al. Third-generation EGFR TKIs: current data and future directions. Mol Cancer. 2018;17:29. doi:10.1186/s12943-018-0778-0.

⁴ Besse B, et al. Presented at the European Society for Medical Oncology (ESMO) Congress; September 13–17, 2024; Barcelona, Spain.

⁵ 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.

⁶ 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.

⁷ 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.

⁸ 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.

⁹ European Medicines Agency. Amivantamab Summary of Product Characteristics. January 2025. Available at: . Accessed September 2025.

¹⁰ 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: . Accessed August 2025.

¹¹ 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: landmark-phase-3-mariposa-study-shows-rybrevantrvamivantamab-plus-lazertinib-resulted-30-percent . Accessed September 2025.

¹² 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.

¹³ 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.

¹⁴ 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.

¹⁵ European Medicines Agency. Amivantamab Summary of Product Characteristics. July 2025. Available at: . Accessed September 2025.

¹⁶ 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.

¹⁷ 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: 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 September 2025.

¹⁸ 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.

¹⁹ European Medicines Agency. Lazcluze. July 2025. Available at: . Accessed September 2025.

²⁰ Global Cancer Observatory. Cancer Today. Available at: . Accessed September 2025.

²¹ Zappa C, et al. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res. 2016;5(3):288–300.

²² Wee P & Wang Z. Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways. Cancers. 2017;9(12):52.

²³ 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.

²⁴ 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.

²⁵ 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.

²⁶ 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.

²⁷ American Lung Association. EGFR and Lung Cancer. Available at: . Accessed September 2025.

²⁸ 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.

²⁹ 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.

³⁰ 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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