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

BEERSE, BELGIUM, 08 February, 2024– The Janssen Pharmaceutical Companies of Johnson & Johnson today announced the submission of a Type II extension of indication application to the European Medicines Agency (EMA) seeking approval of RYBREVANT®▼ (amivantamab), in combination with lazertinib, for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with common epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or exon 21 L858R (L858R) substitution mutations. “Patients with NSCLC with common EGFR mutations face a five-year survival rate of just 19 percent. This, coupled with the significant physical and emotional burden of the disease, reinforces the high unmet medical need we must urgently address,” said Catherine Taylor, Vice President, EMEA Medical Affairs, Therapy Area Strategy, Janssen-Cilag AG. “We are deeply committed to researching and investing in novel targeted therapies to improve the treatment of lung cancer and offer new hope for patients with this condition.” MARIPOSA (NCT04487080) is a randomised, Phase 3 study evaluating amivantamab in combination with lazertinib compared to osimertinib as first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or L858R substitution mutations.7The MARIPOSA study met its primary endpoint, resulting in a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for the combination of amivantamab and lazertinib versus osimertinib, as assessed by blinded independent central review (BICR).1The safety profile of amivantamab plus lazertinib was consistent with prior reports of the combination, with mostly Grade 1 or 2 adverse events (AEs) being reported.1 “Today’s submission is testament to our steadfast dedication to advancing innovative therapies for those who need them most, now and in the future,” said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Janssen Research & Development, LLC. “Pending approval, this novel combination of amivantamab and lazertinib has the potential to transform first-line treatment for patients with EGFR-mutated NSCLC.” The pivotal data from the MARIPOSA studywere featuredin a Presidential Symposium session (Abstract #LBA14) at the 2023 European Society of Medical Oncology (ESMO) Congress.1In December 2023, Janssensubmitted a marketing authorisationapplication (MAA) to the EMA seeking approval of lazertinib, in combination with amivantamab, for the equivalent first-line combination treatment indication based on the MARIPOSA study, with further European Commission (EC) approvals expected in the future. 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 L858R substitution mutations.1,6The primary endpoint of the study is PFS (using RECIST v1.1 guidelines‡) as assessed by BICR.1Secondary endpoints include overall survival (OS), overall response rate (ORR), duration of response (DOR), second progression free survival (PFS2) and intracranial PFS.1 The MARIPOSA study required all patients to have serial brain imaging with MRIs in order to detect or monitor brain metastases, a measure not implemented in most prior studies for EGFR-mutated NSCLC.1The primary endpoint of PFS in MARIPOSA included these central nervous system (CNS) events detected by serial brain MRIs.1Extracranial PFS, which may more closely approximate what would be seen in other trials, was also explored in MARIPOSA.1 About Amivantamab Amivantamab is a fully-human EGFR-MET bispecific antibody with immune cell-directing activity that targets tumours with activating and resistance EGFR mutations and MET mutations and amplifications.2,3,4,5,6 The European Commission granted conditional marketing authorisation of amivantamab in December 2021 for the treatment of adult patients with advanced NSCLC with activating epidermal growth factor receptor (EGFR) exon 20 insertion mutations, after failure of platinum-based therapy.2Amivantamab is the first approved treatment in the European Union specifically targeting EGFR exon 20 insertion mutations for NSCLC.2In October 2023, a type II extension of indication application wassubmittedto the EMA seeking approval of amivantamab in combination with chemotherapy (carboplatin-pemetrexed) for the first-line treatment of patients with NSCLC with EGFR exon 20 insertion mutations.8This was followed, in November 2023, with thesubmissionof a second type II extension of indication application seeking approval of amivantamab in combination with chemotherapy (carboplatin and pemetrexed) for the treatment of adult patients with advanced NSCLC with EGFR ex19del or L858R substitution mutations, after failure of prior therapy including a third-generation EGFR TKI.9 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.7 ▼In line with EMA regulations for new medicines and those given conditional approval, amivantamab is subject to additional monitoring. About 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. An analysis of the efficacy and safety of lazertinib from the Phase 3 study LASER301 was published inThe Journal of Clinical Oncologyin 2023.10In 2018, Janssen Biotech, Inc., entered into a license and collaboration agreement with Yuhan Corporation for the development of lazertinib. About Non-Small Cell Lung Cancer In Europe, over 477,500 patients were diagnosed with lung cancer in 2020.11NSCLC accounts for 85 percent of all lung cancer cases.12Lung cancer is Europe’s biggest cancer killer, with more deaths than breast cancer and prostate cancer combined.11 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.12Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.12,13EGFR 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.14,15,16,17EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.18The five-year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR TKIs is less than 20 percent.19,20Patients with EGFR ex19del or L858R mutations have a real-world five-year OS of 19 percent.21In addition, it has been demonstrated that approximately 50 percent of patients with NSCLC will develop brain metastases which are a substantial contributor to overall cancer mortality.22,23,24 About the Janssen Pharmaceutical Companies of Johnson & Johnson At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Oncology, Immunology, Neuroscience, Cardiovascular, Pulmonary Hypertension, and Retina. Learn more atwww.jnj.com/innovativemedicine/emea/Follow us athttps://www.linkedin.com/company/jnj-innovative-medicine-emea/for our latest news. Janssen Pharmaceutica NV, Janssen-Cilag AG, Cilag GmbH International,and Janssen Research & Development, LLC 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 Pharmaceutica NV, Janssen Research and Development, LLC,Janssen Biotech, Inc.,Janssen-Cilag AG, Cilag GmbH International, 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; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes in behavior 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 January 1, 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 Pharmaceutica NV, Janssen Research and Development, LLC, Janssen Biotech, Inc., Janssen-Cilag AG, Cilag GmbH International, nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. # # # Media Contacts: Zayn Qureshi +44 7760 334666 Email:[email protected] Investor Relations: Raychel Kruper Email:[email protected] ‡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. 1Cho BC P, et al. Amivantamab Plus Lazertinib vs Osimertinib as First-line Treatment in Patients With EGFR-mutated, Advanced Non-small Cell Lung Cancer (NSCLC): Primary Results From MARIPOSA, a Phase 3, Global, Randomized, Controlled Trial. 2023 European Society for Medical Oncology. October 23, 2023. 2Grugan, 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. 3Yun, 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. 4Vijayaraghavan, 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. 5Moores, 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. 6ClinicalTrials.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://clinicaltrials.gov/ct2/show/NCT04487080. Accessed December 2023. 7European Medicines Agency. Amivantamab Summary of Product Characteristics. January 2023. Available at:Rybrevant, INN-amivantamab (europa.eu).Accessed: December 2023. 8J&J.com. Janssen Submits Application to the European Medicines Agency for RYBREVANT®▼ (amivantamab) in Combination with Chemotherapy for the FirstLine Treatment of Adult Patients with Advanced Non-Small Cell Lung Cancer with Activating EGFR Exon 20 Insertion Mutations. Available at:https://www.investor.jnj.com/files/doc_news/2023/Oct/06/amivantamab-papillon-ema-filing-release.pdf. Accessed December 2023. 9Janssen EMEA. Janssen Submits Application to the European Medicines Agency for RYBREVANT®▼ (amivantamab) in Combination with Chemotherapy for the Treatment of Adult Patients with Advanced EGFR-Mutated Non-Small Cell Lung Cancer After Failure of Prior Therapy . Available at:https://www.janssen.com/emea/sites/www_janssen_com_emea/files/janssen_mariposa-2_filing_press_release_2023.pdf. Accessed December 2023. 10Cho, BC, et al. Lazertinib versus gefitinib as first-line treatment in patients withEGFR-mutated advanced non-small-cell lung cancer: Results From LASER301. J Clin Oncol. 2023;41(26):4208-4217. 11Globocan 2020. Estimated number of incident cases deaths in 2020, Europe, both sexes, all ages. Available at:www.gco.iarc.fr. Accessed December 2023. 12Zappa C et al. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res 2016;5(3): 288–300. 13Wee, P & Wang, Z. Cancers 2017. Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways Volume: 9 Issue: 12 Pages: 52. 14Pennell NA, et al. A phase II trial pf adjuvant erlotinib in patients with resected epidermal growth factor receptor-mutant non-small cell lung cancer.J Clin Oncol. 37:97-104. 15Burnett 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; January 29, 2021; Singapore. 16Zhang 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. 17Midha 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. 18American Lung Association.EGFR and Lung Cancer.https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/egfr. Accessed October 2023. 19Howlader N, et al. SEER Cancer Statistics Review, 1975-2016, National Cancer Institute. Bethesda, MD,https://seer.cancer.gov/csr/1975_2016/, based on December 2018 SEER data submission, posted to the SEER web site. 20Lin JJ, et al. Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs.J Thorac Oncol. 2016 Apr;11(4):556-65. 21Girard N, et al. Comparative clinical outcomes for patients with NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore. 22Shao J et al. The number of brain metastases predicts the survival of non-small cell lung cancer patients with EGFRR mutation status.Cancer Rep (Hoboken).2022;5(9): e1550. 23Achrol A et al. Brain metastases.Nat Rev Dis Primers. 2019;17(5): 5. 24Rangachari D et al. Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers.Lung Cancer. 2015;88(1): 108-111. Oncology Discover J&J News Our Credo & our purpose Leadership Social impact Suppliers Our history Policies & reports Environmental sustainability Medicines & therapies Products Oncology Immunology Neuroscience Cardiopulmonary Medical devices & technology Products Cardiovascular Orthopaedics Surgery Vision About us Our company Medicines & therapies Medical devices & technology Careers Investors Media Key links Terms of use Privacy Cookie policy Customize cookie settings Digital Accessibility Statement Get in touch Contact Socials linkedin instagram facebook twitter This website is intended for U.S. audiences only. 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