Investigational chemotherapy-free regimen of amivantamab plus lazertinib addresses a significant unmet need as most patients with EGFR-mutated NSCLC have high-risk disease1 Landmark Phase 3 MARIPOSA data featured in an oral presentation at ASCO1 BEERSE, BELGIUM, May 31, 2024 (GLOBE NEWSWIRE) — Janssen-Cilag International NV, a Johnson & Johnson company, today announced new data from the Phase 3 MARIPOSA study demonstrating the efficacy of first-line treatment with RYBREVANT®▼ (amivantamab) in combination with lazertinib in patients with high-risk disease or clinical features, which occur in nearly 85 percent of patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations.1,2 Results from the new analysis show the amivantamab-combination consistently and significantly improved progression free survival (PFS) compared to osimertinib in patients with NSCLC with EGFR exon 19 deletion (ex19del) or L858R mutations.1 These data were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #8504) taking place in Chicago, Illinois from 31 May – 4 June 2024.1 “These new data demonstrate the efficacy of amivantamab plus lazertinib, showing a significant reduction in the risk of disease progression or death compared to osimertinib in several high-risk subgroups of patients with EGFR-mutated NSCLC,” said Byoung Chul Cho, M.D., Ph.D, medical oncologist and professor in the Division of Medical Oncology at Yonsei Cancer Center, Yonsei University College of Medicine in Seoul, Republic of Korea, and the study author.* “These findings support the potential of this combination as an important first-line option for these patients who face significant unmet needs.” The MARIPOSA study enrolled treatment-naïve patients with EGFR-mutant (ex19del or L858R) advanced NSCLC.1 Overall, results showed amivantamab plus lazertinib resulted in a significant reduction in the risk of disease progression or death compared to osimertinib as previously reported.1 High-risk features, such as liver or brain metastases, baseline TP53 co-mutations, and circulating tumour DNA (ctDNA) shedding are common in patients with EGFR-mutated advanced NSCLC and associated with poor prognoses.3,4,5,6 In the study, 89 percent of enrolled patients had one or more of these high-risk disease or clinical features at baseline. Specifically, 41 percent had brain metastases, 16 percent had liver metastases, 54 percent had TP53 co-mutations, 70 percent had ctDNA present at baseline and 15 percent continued to shed ctDNA after two cycles of treatment.1 Results from the analysis showed treatment with amivantamab plus lazertinib significantly reduced the risk of disease progression or death consistently across all high-risk subgroups:1 31 percent compared to osimertinib in patients with a history of brain metastases (18.3 vs 13.0 months; hazard ratio [HR], 0.69; [95 percent confidence interval [CI], 0.53-0.92]; P=0.010)42 percent compared to osimertinib in patients with liver metastases at baseline (18.2 vs 11.0 months; HR, 0.58 [95 percent CI, 0.37-0.91]; P=0.017)35 percent compared to osimertinib among patients with TP53 co-mutations (18.2 vs 12.9 months; HR, 0.65 [95 percent CI, 0.48-0.87]; P=0.003) 32 percent compared to osimertinib in patients with detectable ctDNA at baseline (20.3 vs 14.8 months; HR, 0.68 [95 percent CI, 0.53-0.86]; P=0.002)51 percent compared to osimertinib in patients without cleared ctDNA at C3D1 (16.5 vs 9.1 months; HR, 0.49 [95 percent CI, 0.27-0.87]; P=0.015) “High-risk features are incredibly prevalent in first-line EGFR-mutated non-small-cell lung cancer and are associated with a poor prognosis,” said Henar Hevia, Ph.D, Senior Director, EMEA Therapeutic Area Lead, Oncology, Johnson & Johnson Innovative Medicine. “The encouraging findings from this study, demonstrating improved progression-free survival in this critical patient subgroup treated with amivantamab and lazertinib, highlight our commitment to pioneering precision medicine and establishing new standards of care for one of the largest lung cancer patient populations.” As reported at the European Society for Medical Oncology (ESMO) 2023 Congress, the safety profile of the combination of amivantamab and lazertinib was consistent with the safety profiles of the individual treatments, with mostly Grade 1 or 2 adverse events (AEs) reported.7 Toxicity was largely manageable with dose interruptions and reductions, along with supportive care measures commonly used in the treatment of patients with NSCLC.7 The most common Grade 3 or higher treatment-related AEs were rash and paronychia.7 Amivantamab plus lazertinib had higher rates of EGFR and MET-related AEs (hypoalbuminemia and peripheral oedema) and venous thromboembolism compared to osimertinib, with higher rates of diarrhoea being observed with osimertinib.7 The rate of discontinuation of all study treatments due to treatment-related AEs for the amivantamab combination was 10 percent.7 The rate of interstitial lung disease (including pneumonitis) was less than three percent in both arms.7 “With the majority of patients with EGFR-mutated lung cancer having high-risk disease and clinical features, ensuring that all patients receive the most appropriate treatment in the first-line setting is critical. The results presented at ASCO suggest amivantamab plus lazertinib may offer a new standard of care in this patient population,” said Craig Tendler, M.D., Vice President, Late Development and Global Medical Affairs, Johnson & Johnson Innovative Medicine. “These new findings continue to demonstrate how amivantamab-based regimens are transforming treatment for patients with EGFR-mutated non-small cell lung cancer and add to the growing body of evidence that supports the potential promise of this chemotherapy-free approach.” #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 first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or L858R substitution mutations.7,8 The primary endpoint of the study is PFS (using RECIST v1.1 guidelines) as assessed by BICR.8 Secondary endpoints include overall survival (OS), overall response rate (ORR), duration of response (DOR), second progression-free survival (PFS2) and intracranial PFS.8 About AmivantamabAmivantamab 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.9,10,11,12 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.13 Amivantamab is the first approved treatment in the European Economic Area specifically targeting EGFR exon 20 insertion mutations for NSCLC.13 In February 2024, a type II extension of indication application was submitted to the European Medicines Agency (EMA) based on the MARIPOSA study for 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) substitution mutations.14 An application to the EMA was also submitted in November 2023 for a 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.15 In April 2024, the Committee for Medicinal Products for Human Use (CHMP) provided a positive opinion for the use of amivantamab in combination with carboplatin and pemetrexed chemotherapy, for the first-line treatment of adult patients with advanced NSCLC with EGFR exon 20 insertion mutations.16 In addition to the MARIPOSA study, amivantamab is being studied in multiple clinical trials in NSCLC, including: The Phase 3 PAPILLON (NCT04538664) study assessing amivantamab in combination with carboplatin-pemetrexed versus chemotherapy alone in the first-line treatment of patients with advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.17The Phase 3 MARIPOSA-2 (NCT04988295) study assessing the efficacy of amivantamab (with or without lazertinib) and carboplatin-pemetrexed versus carboplatin-pemetrexed alone in patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC after disease progression on or after osimertinib.18The Phase 1 CHRYSALIS (NCT02609776) study evaluating amivantamab in patients with advanced NSCLC.19The Phase 1/1b CHRYSALIS-2 (NCT04077463) study evaluating amivantamab in combination with lazertinib and lazertinib as a monotherapy in patients with advanced NSCLC with EGFR mutations.20The Phase 1 PALOMA (NCT04606381) study assessing the feasibility of subcutaneous administration of amivantamab based on safety and pharmacokinetics and to determine a dose, dose regimen and formulation for amivantamab subcutaneous delivery.21The Phase 2 PALOMA-2 (NCT05498428) study assessing subcutaneous amivantamab in patients with advanced or metastatic solid tumours including EGFR-mutated NSCLC.22The Phase 3 PALOMA-3 (NCT05388669) study assessing lazertinib with subcutaneous amivantamab compared to intravenous amivantamab in patients with EGFR-mutated advanced or metastatic NSCLC.23The Phase 1/2 METalmark (NCT05488314) study assessing amivantamab and capmatinib combination therapy in locally advanced or metastatic NSCLC.24The Phase 1/2 PolyDamas (NCT05908734) study assessing amivantamab and cetrelimab combination therapy in locally advanced or metastatic NSCLC.25 The Phase 2 SKIPPirr study (NCT05663866) exploring how to decrease the incidence and/or severity of first-dose infusion-related reactions with amivantamab in combination with lazertinib in relapsed or refractory EGFR-mutated advanced or metastatic NSCLC.26 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 EMA regulations for new medicines, amivantamab 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 2022.27 NSCLC accounts for 85 percent of all lung cancer cases.28 Lung cancer is Europe’s biggest cancer killer, with more deaths than breast cancer and prostate cancer combined.27 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.28 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.28,29 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.30,31,32,33 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.34 The five year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR tyrosine kinase inhibitors (TKIs) is less than 20 percent.35,36 EGFR exon 20 insertion mutations are the third most prevalent activating EGFR mutation.37 Patients with EGFR exon 20 insertion mutations have a real-world five-year overall survival (OS) of eight percent in the frontline setting, which is worse than patients with EGFR ex19del or L858R mutations, who have a real-world five-year OS of 19 percent.38 In 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.3,39,40 Learn more at www.janssen.com/emea. Follow us at www.linkedin.com/company/jnj-innovative-medicine-emea. Janssen-Cilag International NV is a Johnson & Johnson company. 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 International NV 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 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 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 International NV, 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. ### *Prof. Byoung Chul Cho has provided consulting, advisory, and speaking services to Janssen-Cilag International NV; he has not been paid for any media work. 1 Felip E, et al. Amivantamab plus lazertinib vs osimertinib in first-line EGFR-mutant advanced non-small cell lung cancer (NSCLC) with biomarkers of high-risk disease: A secondary analysis from the phase 3 MARIPOSA study. 2024 American Society for Clinical Oncology Annual Meeting. 31 May, 2024. 2 Felip E, et al. Amivantamab plus lazertinib vs osimertinib in first-line EGFR-mutant advanced non-small cell lung cancer (NSCLC) with biomarkers of high-risk disease: A secondary analysis from the phase 3 MARIPOSA study. Abstract. 2024 American Society for Clinical Oncology Annual Meeting. 31 May, 2024. 3 Shao J et al. The number of brain metastases predicts the survival of non-small cell lung cancer patients with EGFR mutation status. Cancer Rep (Hoboken). 2022 Sep;5(9):e1550. 4 Stockhammer P, et al. Co-Occurring Alterations in Multiple Tumor Suppressor Genes Are Associated With Worse Outcomes in Patients With EGFR-Mutant Lung Cancer. J Thorac Oncol. 2024 Feb;19(2):240-251. 5 Chen Y, et al. Analysis of metastases in non-small cell lung cancer patients with epidermal growth factor receptor mutation. Ann Transl Med. 2021 Feb;9(3):206. 6 Russo A, et al. Influence of EGFR mutational status on metastatic behavior in non squamous non small cell lung cancer. Oncotarget. 2017 Jan 31;8(5):8717-8725. 7 Cho BC, 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. 23 October, 2023. 8 ClinicalTrials.gov. A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in LocallyAdvanced or Metastatic Non-Small Cell Lung Cancer (MARIPOSA). Available at: https://classic.clinicaltrials.gov/ct2/show/NCT04487080. Accessed: May 2024. 9 Grugan, 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. 10 Yun, 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. 11 Vijayaraghavan, 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. 12 Moores, 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 European Medicines Agency. Amivantamab Summary of Product Characteristics. January 2023. Available at: Rybrevant, INN-amivantamab (europa.eu). Accessed: May 2024. 14 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 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 Accessed: May 2024. 15 Janssen 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: May 2024. 16 Janssen.com/EMEA. Johnson & Johnson receives positive CHMP opinion for RYBREVANT®▼ (amivantamab) in combination with chemotherapy for the first-line treatment of patients with advanced non-small cell lung cancer with activating EGFR exon 20 insertion mutations. Available at: https://www.janssen.com/emea/sites/www_janssen_com_emea/files/papillon_chmp_press_release_2024.pdf Accessed: May 2024. 17 ClinicalTrials.gov. A Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Characterized by Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions (PAPILLON). Available at: https://clinicaltrials.gov/ct2/show/NCT04538664. Accessed May 2024. 18 ClinicalTrials.gov. A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Osimertinib Failure (MARIPOSA-2). Available at: https://classic.clinicaltrials.gov/ct2/show/study/NCT04988295. Accessed May 2024. 19 ClinicalTrials.gov. A Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer (CHRYSALIS). https://clinicaltrials.gov/ct2/show/NCT02609776. Accessed May 2024. 20 ClinicalTrials.gov. A Study of Lazertinib as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer (CHRYSALIS-2). https://clinicaltrials.gov/ct2/show/NCT04077463. Accessed May 2024. 21 ClinicalTrials.gov. A Study of Amivantamab Subcutaneous (SC) Administration for the Treatment of Advanced Solid Malignancies (PALOMA). Available at: https://clinicaltrials.gov/study/NCT04606381. Accessed May 2024. 22 ClinicalTrials.gov. A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (PALOMA-2). https://clinicaltrials.gov/ct2/show/NCT05498428. Accessed May 2024. 23 ClinicalTrials.gov. A Study of Lazertinib With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Participants With Epidermal Growth Factor Receptor (EGFR)-Mutated Advanced or Metastatic Non-small Cell Lung Cancer (PALOMA-3). https://clinicaltrials.gov/ct2/show/NCT05388669. Accessed May 2024. 24 ClinicalTrials.gov. A Study of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer (METalmark). https://clinicaltrials.gov/ct2/show/NCT05488314. Accessed May 2024. 25 ClinicalTrials.gov. A Study of Combination Therapy With Amivantamab and Cetrelimab in Participants With Metastatic Non-small Cell Lung Cancer (PolyDamas). https://www.clinicaltrials.gov/study/NCT05908734?term=polydamas&rank=1. Accessed May 2024. 26 ClinicalTrials.gov. Premedication to Reduce Amivantamab Associated Infusion Related Reactions (SKIPPirr). https://classic.clinicaltrials.gov/ct2/show/NCT05663866. Accessed May 2024. 27 Global Cancer Observatory. Cancer Today. Available at: https://gco.iarc.fr/en. Accessed: May 2024. 28 Zappa C, et al. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res 2016;5(3):288–300. 29 Wee, P & Wang, Z. Cancers 2017. Epidermal Growth Factor Receptor Cell Proliferation Signaling PathwaysVolume: 9 Issue: 12 Pages: 52. 30 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. 37:97-104. 31 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; 29 January, 2021; Singapore. 32 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. 33 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. 34 American Lung Association. EGFR and Lung Cancer. https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/egfr. Accessed May 2024. 35 Howlader N, et al. SEER Cancer Statistics Review, 1975-2016, National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975_2016/, based on November 2018 SEER data submission, posted to the SEER web site. 36 Lin 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. 37 Arcila, M. et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther. 2013 Feb; 12(2):220-9. 38 Girard 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. 39 Achrol A et al. Brain metastases. Nat Rev Dis Primers. 2019;17(5): 5. 40 Rangachari 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. CP-455161May 2024