Median overall survival not yet reached with a projected improvement of more than one year versus osimertinib*1
BEERSE, BELGIUM, March 26, 2025 (GLOBE NEWSWIRE) -- Janssen-Cilag International NV, a Johnson & Johnson company, today announced results for the gold standard endpoint in cancer treatment of overall survival (OS) from the Phase 3 MARIPOSA study. Head-to-head comparison data versus osimertinib showed RYBREVANT®▼(amivantamab) plus LAZCLUZE®▼(lazertinib) significantly extended OS in the first-line treatment of patients with 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 Median OS is projected to exceed one year* beyond the median of three years observed with osimertinib, and has not yet been reached.1 This is the first study to show a statistically significant and clinically meaningful OS improvement versus osimertinib.1 These new data were presented during a proffered paper session at the 2025 European Lung Cancer Congress (ELCC) (Abstract #4O).1
“The survival curve demonstrates that amivantamab plus lazertinib can help patients live longer compared to osimertinib monotherapy, and suggests the benefit keeps growing over time,” said trial investigator Professor Nicolas Girard**, M.D., Ph.D., Head of Medical Oncology, Institut Curie, and Professor of Thoracic Oncology and Respiratory Medicine at the Paris Saclay University, France. “We see the gap between the survival curves continue to widen, which is exactly what we want to see in lung cancer treatment to improve outcomes for patients. These results reinforce that we are entering a new era for EGFR-mutated advanced non-small cell lung cancer.”
Unlike progression-free survival (PFS), which tracks the time a treatment keeps a patient’s cancer from progressing, overall survival may help patients understand the impact therapy could have on the ability to live longer from the start of treatment.2,3 Extending life expectancy is the most meaningful indicator of a treatment’s impact.4
“We are committed to redefining the standard of care for people living with lung cancer and are excited to be at a point where that is becoming a reality,” said Henar Hevia, PhD., Senior Director, EMEA Therapeutic Area Lead, Oncology, Johnson & Johnson Innovative Medicine. “The overall survival results from the MARIPOSA study reinforce the potential life-changing impact the chemotherapy-free combination of amivantamab and lazertinib can have for patients and their loved ones, when used in the first-line setting.”
At a median follow-up of 37.8 months, patients treated with first-line amivantamab plus lazertinib had a significantly longer overall survival compared to those receiving osimertinib (hazard ratio [HR], 0.75; 95 percent Confidence Interval [CI], 0.61-0.92; nominal P<0.005†).1 Median OS for amivantamab plus lazertinib has not yet been reached, indicating that survival benefits continue to extend beyond the measured follow-up period (Not Reached [NR]; 95 percent CI, 42.9-NR).1 Comparatively, median OS for osimertinib-treated patients was 36.7 months (95 percent CI, 33.4-41.0) and consistent with prior studies with osimertinib.1,5 Fifty-six percent of patients treated with amivantamab and lazertinib were alive at three and a half years compared to 44 percent of patients on osimertinib, the current standard of care.1 Projections based on survival data suggest amivantamab plus lazertinib could extend median OS by at least 12 months compared to osimertinib*.1
The amivantamab plus lazertinib combination also prolonged multiple secondary endpoints vs osimertinib, including intracranial PFS, intracranial duration of response and intracranial overall response rate.1 Notably, amivantamab plus lazertinib prolonged time to symptomatic progression (TTSP) – the time from treatment randomisation to the onset of new or worsening lung cancer symptoms requiring intervention – by more than 14 months compared to osimertinib (43.6 months vs 29.3 months; HR, 0.69; 95 percent CI, 0.57-0.83; nominal P<0.001†).1 This is a key patient-centered measure, highlighting how long quality of life can be preserved before lung cancer symptoms further impact patient care.6
“Right now, approximately twenty percent of patients with EGFR-mutated advanced NSCLC survive beyond five years. These MARIPOSA results suggest that amivantamab plus lazertinib can help change this statistic,” said Joshua Bauml, M.D., Vice President, Lung Cancer Disease Area Stronghold Leader, Johnson & Johnson Innovative Medicine. “By using this regimen in first-line treatment, we’re offering the potential to delay the need for chemotherapy and give patients and their families hope for more time.”
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, except diarrhoea, for which rates were higher for osimertinib.1 The most common Grade 3 or higher adverse events (AEs) were rash (17 percent), paronychia (12 percent), dermatitis acneiform (9 percent) and alanine transaminase increase (7 percent).1 Most AEs occurred early during amivantamab and lazertinib treatment.1 Findings from other studies with amivantamab suggest that implementing prophylactic measures during the first four months of amivantamab and lazertinib treatment may significantly reduce the risk of skin reactions, infusion-related reactions and venous thromboembolic events.7,8,9,10
The MARIPOSA study met its primary endpoint in October 2023, showing a statistically significant and clinically meaningful improvement in PFS compared to osimertinib.11,12
Amivantamab plus lazertinib is approved in the European Union for the first-line treatment of patients with advanced common EGFR-mutated NSCLC.13 These OS results will be shared with health authorities globally.
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 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.14 The primary endpoint of the study is PFS (using RECIST v1.1 guidelines‡) as assessed by BICR.14 Secondary endpoints include overall survival (OS), overall response rate (ORR), duration of response (DOR), second progression free survival (PFS2) and intracranial PFS.14
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.13,15,16,17
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.
In February 2025, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended an extension of marketing authorisation for a subcutaneous (SC) formulation of amivantamab, in combination with lazertinib for the first-line treatment of adult patients with advanced NSCLC with exon 19 deletions or exon 21 L858R substitution mutations, and as a monotherapy for the treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy.18 This extension is currently pending EC approval.
Subcutaneous amivantamab is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug delivery technology.19
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 while sparing wild-type EGFR.20 An analysis of the efficacy and safety of lazertinib from the Phase 3 study LASER301 was published in The Journal of Clinical Oncology in 2023.20
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.21
▼ 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 2022.22 NSCLC accounts for 85 percent of all lung cancer cases.23 Lung cancer is Europe’s biggest cancer killer, with more deaths than breast cancer and prostate cancer combined.22
The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.23 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.23,24 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.25,26,27,28 EGFR ex19del or EGFR exon 21 L858R mutations are the most common EGFR mutations.29 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.30,31,32
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 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 Janssen-Cilag International NV, Janssen Biotech, Inc., Janssen-Cilag, S.A. and/or 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; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; 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 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. None of Janssen-Cilag International NV, Janssen Biotech, Inc., Janssen-Cilag, S.A. nor Johnson & Johnson undertakes 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.
*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.
**Professor Nicolas Girard has served as a consultant to Janssen-Cilag International NV; he has not been paid for any media work.
†P-value is calculated by log-rank test stratified by mutation type (Ex19del or L858R), race (Asian or Non-Asian), and history of brain metastasis (present or absent).
‡ RECIST (version 1.1) 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.
References
1 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.
2 NCI Dictionary of Cancer Terms. Overall survival. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/overall-survival. Accessed March 2025.
3 Hess LM,et al. Relationship between Progression-free Survival and Overall Survival in Randomized Clinical Trials of Targeted and Biologic Agents in Oncology. J Cancer. 2019 Jun 9;10(16):3717-3727.
4 Delgado A & Guddati AK. Clinical endpoints in oncology - a primer. Am J Cancer Res. 2021 Apr 15;11(4):1121-1131.
5 Valdiviezo, N, et al. First-line (1L) osimertinib (osi) ± platinum-pemetrexed in EGFR-mutated (EGFRm) advanced NSCLC: FLAURA2 post-progression outcomes. Ann. Oncol. 2024 March; 9: 1-53.
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7 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 February 13, 2025.
8 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.
9 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.
10 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.
11 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 March 2025
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13 European Medicines Agency. Amivantamab Summary of Product Characteristics. January 2025. Available at: https://www.ema.europa.eu/en/documents/product-information/rybrevant-epar-product-information_en.pdf. Accessed March 2025.
14 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 March 2025.
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18 innovativemedicine.jnj.com/EMEA. CHMP recommends subcutaneous RYBREVANT®▼ (amivantamab) for the treatment of patients with advanced EGFR-mutated non-small cell lung cancer. Available at: https://innovativemedicine.jnj.com/emea/newsroom/chmp-recommends-subcutaneous-rybrevant-amivantamab-for-the-treatment-of-patients-with-advanced-egfr-mutated-non-small-cell-lung-cancer. Accessed March 2025.
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