RYBREVANT®▼ (amivantamab) plus lazertinib show strong favourable overall survival trend versus osimertinib in EGFR-mutated advanced lung cancer

New longer-term data from the MARIPOSA study confirm superior outcomes of amivantamab plus lazertinib regimen compared to osimertinib monotherapy as first-line therapy1 Results from an interim analysis featured in late-breaker oral presentation at WCLC1 BEERSE, Belgium, Sept. 08, 2024 (GLOBE NEWSWIRE) — Janssen-Cilag International NV, a Johnson & Johnson company, today announced longer follow-up data from the landmark Phase 3 MARIPOSA study which showed first-line treatment with RYBREVANT®▼ (amivantamab) combined with lazertinib provided consistent benefit across long-term outcomes compared to osimertinib monotherapy in adult patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations.1 The data show a strong and improving overall survival (OS) trend favouring amivantamab plus lazertinib at approximately three years of follow-up.1 These results were presented in a late-breaking oral presentation at the International Association for the Study of Lung Cancer (IASLC) 2024 World Conference on Lung Cancer (WCLC) taking place in San Diego, California from 7-10 September (Abstract #1146).1 At three years (median follow-up of 31.1 months), 61 percent of patients receiving amivantamab plus lazertinib were alive compared to 53 percent of those treated with osimertinib based on an analysis performed at the request of a health authority* (Median OS not estimable [NE] vs 37.3 months; hazard ratio [HR]=0.77; 95 percent confidence interval [CI], 0.61-0.96; nominal P=0.019).1 Overall survival will continue to be assessed with longer term follow-up as a key secondary endpoint.2 The primary efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review (BICR).1 “By combining the multi-targeted mechanism of amivantamab with lazertinib, a central nervous system penetrant third-generation tyrosine kinase inhibitor, we are advancing a chemotherapy-free regimen for the first-line treatment of patients with EGFR-mutant NSCLC. This approach blocks EGFR and MET pathways and leverages the immune system, offering patients an opportunity for prolonged benefits,” said Shirish M. Gadgeel, M.D., Chief of Division of Hematology and Oncology, Associate Director at Henry Ford Cancer Institute and presenting author.** “Even more encouraging is the marked improvement in the hazard ratio and the ongoing separation of survival curves, showing an eight percent improvement at three years for amivantamab plus lazertinib compared to osimertinib. This supports the long-term benefit of the combination as a first-line treatment option in this setting.” Results further showed amivantamab plus lazertinib demonstrated a trend toward improved central nervous system disease control compared to osimertinib at three years (HR=0.82; 95 percent CI, 0.62-1.09; nominal P=0.165).1 At the three-year landmark, intracranial PFS was double for amivantamab plus lazertinib versus osimertinib (38 percent vs 18 percent, respectively).1 More patients remained on treatment at three years with the amivantamab combination compared to osimertinib (40 percent vs 29 percent, respectively; HR=0.80; 95 percent CI, 0.68-0.96; nominal P=0.014).1 Additionally, more patients receiving amivantamab and lazertinib at the three-year follow up had not started a subsequent therapy versus osimertinib (45 percent vs 32 percent, respectively; HR=0.77; 95 percent CI, 0.65-0.93; nominal P=0.005).1 Progression-free survival after first subsequent therapy was 57 percent for the amivantamab combination compared to 49 percent for osimertinib (HR=0.73; 95 percent CI, 0.59-0.91; nominal P=0.004).1  “At Johnson & Johnson, we are dedicated to advancing lung cancer care, with a focus on delivering precision therapies that can improve outcomes from the earliest stages of treatment,” said Henar Hevia, Ph.D., Senior Director, EMEA Therapeutic Area Lead, Oncology, Johnson & Johnson Innovative Medicine. “These longer-term follow-up results from the MARIPOSA study add to the compelling body of evidence supporting the combination of amivantamab and lazertinib as a potential first-line treatment regimen for patients with EGFR-mutated advanced non-small cell lung cancer.” “Promising results like these presented at WCLC reinforce our mission to improve the lives of patients diagnosed with lung cancer,” said Joshua Bauml, M.D., Vice President, Lung Cancer Disease Area Stronghold Leader, Johnson & Johnson Innovative Medicine. “We are encouraged by the favourable overall survival trend observed with amivantamab plus lazertinib and are eager to see how these data evolve as we continue to follow patients over time.”  As previously reported in the MARIPOSA study, the safety profile was consistent with previous reports from Phase 1-2 studies.2 The rate of discontinuation of all study treatments due to treatment-related adverse events for amivantamab plus lazertinib was 10 percent and 3 percent with osimertinib.2 The rate of interstitial lung disease (including pneumonitis) was approximately three percent in both arms.2 #ENDS# About the MARIPOSA StudyMARIPOSA (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 the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or L858R substitution mutations.2,3 The primary endpoint of the study is PFS (using RECIST v1.1 guidelines) as assessed by BICR.3 Secondary endpoints include overall survival (OS), overall response rate (ORR), duration of response (DOR), second progression-free survival (PFS2) and intracranial PFS.3 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.4,5,6,7 The European Commission (EC) has granted marketing authorisation of amivantamab in the following indications:8 In combination with carboplatin and pemetrexed, for the first-line treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutationsAs monotherapy, for treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations, after failure of platinum-based therapyIn combination in with carboplatin and pemetrexed, for the treatment of adult patients with advanced NSCLC with EGFR exon 19 deletions or L858R substitution mutations, after failure of prior therapy including an EGFR TKI In February 2024, a Type II extension of indication application was submitted to the EMA based on the MARIPOSA study, for amivantamab in combination with lazertinib for the first-line treatment of adult patients with advanced NSCLC with common EGFR ex19del or L858R substitution mutations.9 In May 2024, an application for the extension of the amivantamab marketing authorisation was submitted seeking approval for the use of a subcutaneous (SC) formulation of amivantamab in combination with lazertinib for the first-line treatment of adult patients with advanced NSCLC with EGFR ex19del or L858R mutations, and for the use of SC amivantamab monotherapy in adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy.10 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.8 ▼ In line with EMA 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. Lazertinib is an oral, third-generation, brain-penetrant EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild-type EGFR.11 An analysis of the efficacy and safety of lazertinib from the Phase 3 study LASER301 was published in The Journal of Clinical Oncology in 2023.11 About Non-Small Cell Lung CancerIn Europe, it is estimated that 484,306 people were diagnosed with lung cancer in 2022.12 NSCLC accounts for 85 percent of all lung cancer cases.13 Lung cancer is Europe’s biggest cancer killer, with more deaths than breast cancer and prostate cancer combined.12 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.13 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.13,14 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.15,16,17,18 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.19 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.20,21,22 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 www.janssen.com/emea. Follow us at www.linkedin.com/company/jnj-innovative-medicine-emea. Janssen Cilag, S.A, Janssen Research & Development, LLC, Janssen-Cilag International NV and Janssen Biotech, Inc., 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 and 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 materialize, actual results could vary materially from the expectations and projections of, Janssen Cilag, S.A, Janssen Research & Development, LLC, Janssen-Cilag International NV, Janssen Biotech, Inc., 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 for the fiscal year ended December 31, 2023, 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 www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of Janssen Cilag, S.A, Janssen Research & Development, LLC, Janssen-Cilag International NV, Janssen Biotech, Inc., 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. 2024. All rights reserved.    *This analysis was requested by health authorities and had nominal alpha spend. A P-value of ≤0.00001 was required for statistical significance.  **Dr. Shirish M. Gadgeel has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work.  1 Gadgeel SM, et al. Amivantamab Plus Lazertinib vs Osimertinib in First-line EGFR-mutant Advanced NSCLC: Longer Follow-up of the MARIPOSA Study. IASLC WCLC 2024. September 8, 2024. 2  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. Last accessed September 2024. 3 ClinicalTrials.gov. A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (MARIPOSA). Available at: https://classic.clinicaltrials.gov/ct2/show/NCT04487080. Accessed September 2024. 4 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. 5 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. 6 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. 7 Vijayaraghavan S, et al. Amivantamab (JNJ-61186372), an Fc Enhanced EGFR/cMet Bispecific Antibody, Induces Receptor Downmodulation and Antitumor Activity by Monocyte/Macrophage Trogocytosis. Mol Cancer Ther 2020;19(10):2044-2056. 8 European Medicines Agency. Amivantamab Summary of Product Characteristics. July 2024. Available at: https://www.ema.europa.eu/en/documents/product-information/rybrevant-epar-product-information_en.pdf. Last accessed September 2024. 9 Janssen.com/EMEA. Janssen Submits Type II Extension of Indication Application to the European Medicines Agency Seeking Approval of RYBREVANT®▼ (amivantamab), in combination with Lazertinib, for the First-Line Treatment of Patients with EGFR Mutated Non-Small Cell Lung Cancer. Available at: https://www.janssen.com/emea/sites/www_janssen_com_emea/files/amivantamab_mariposa_ema_filing_release_2024_2.pdf. Last accessed September 2024. 10 Janssen.com/EMEA. Johnson & Johnson submits application to the European Medicines Agency seeking approval of subcutaneous formulation of RYBREVANT®▼ (amivantamab) for the treatment of patients with EGFR-mutated non-small cell lung cancer. Available at: https://www.globenewswire.com/news-release/2024/05/31/2891769/0/en/Johnson-Johnson-submits-application-to-the-European-Medicines-Agency-seeking-approval-of-subcutaneous-formulation-of-RYBREVANT-amivantamab-for-the-treatment-of-patients-with-EGFR-m.html. Last accessed September 2024. 11 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. 12 Global Cancer Observatory. Cancer Today. Available at: https://gco.iarc.who.int/media/globocan/factsheets/populations/908-europe-fact-sheet.pdf. Last accessed September 2024. 13 Zappa C, et al. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res 2016;5(3):288–300. 14 Wee P & Wang Z. Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways. Cancers 2017;9(12):52. 15 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. 16 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. 17 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. 18 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. 19 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. Last accessed September 2024. 20 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. 21 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. 22 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. CP-473379September 2024 FOR EUROPEAN MEDICAL AND PHARMACEUTICAL TRADE MEDIA ONLY CONTACT: Media contact:
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