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

Early data show an overall survival trend favoring the combination of amivantamab and lazertinib compared to osimertinib; consistent results seen in patients with and without brain metastases1 Late-breaking results from the MARIPOSA study featured in a Presidential Symposium at 2023 ESMO Congress1 BEERSE, BELGIUM, Oct. 23, 2023 (GLOBE NEWSWIRE) — The Janssen Pharmaceutical Companies of Johnson & Johnson today announced results from the Phase 3 MARIPOSA study showing RYBREVANT®▼ (amivantamab) in combination with lazertinib compared to osimertinib resulted in a 30 percent reduction in the risk of disease progression or death (Hazard Ratio [HR]=0.70; 95 percent Confidence Interval [CI], 0.58–0.85; P<0.001) in the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with either epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution.1 Results also showed a favourable trend in overall survival (OS) for amivantamab and lazertinib in these patients compared to osimertinib (HR=0.80; 95 percent CI, 0.61–1.05; P=0.11) at a first interim analysis.1 These data were presented in a Presidential Symposium at the European Society for Medical Oncology (ESMO) 2023 Congress taking place 20-24 October in Madrid, Spain (Abstract #LBA14).1 “Despite advances in EGFR-mutated NSCLC treatment, novel targeted therapies and regimens are needed to address resistance and disease progression, which are nearly inevitable with current treatments,” 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 presenting author. “With the combination of amivantamab and lazertinib in the MARIPOSA study, progression free survival was significantly improved in patients with previously untreated EGFR-mutated NSCLC compared to osimertinib. These results support the potential of this amivantamab combination to be a future standard of care.” At a median follow-up of 22 months, median progression-free survival (PFS) for amivantamab and lazertinib was 23.7 months compared to 16.6 months for osimertinib (HR=0.70; 95 percent CI, 0.58–0.85; P<0.001).1 Other secondary endpoints showed consistent and clinically meaningful benefits for the combination of amivantamab and lazertinib versus osimertinib across prespecified patient subgroups, including race, type of EGFR mutation, history of brain metastasis, and performance status.1† Lazertinib was included in the MARIPOSA study to determine its contribution to the combination with amivantamab, and lazertinib monotherapy was shown to provide a clinically meaningful median PFS of 18.5 months (95 percent CI, 14.8–20.1).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.1 The primary endpoint of PFS in MARIPOSA included these central nervous system (CNS) events detected by serial brain MRIs.1 Extracranial PFS, which may more closely approximate what would be seen in other trials, was also explored in MARIPOSA.1 The median PFS when censoring CNS-only first progressions was 27.5 months for the combination of amivantamab and lazertinib, compared with 18.5 months for osimertinib (HR=0.68; 95% CI, 0.56–0.83; P<0.001).1 The median duration of response (DOR), or the length of time that a tumour continues to respond to treatment without the cancer growing or spreading, was significantly longer for patients receiving amivantamab plus lazertinib compared to osimertinib, with a nine-month improvement in median DOR (25.8 vs. 16.8 months).1 “Lung cancer remains the leading cause of cancer death worldwide and for patients with certain oncogenic driver mutations, the survival rate with the current standard of care, tyrosine kinase inhibitors, is still too low,” said Martin Vogel, EMEA Therapeutic Area Lead Oncology, Janssen-Cilag GmbH. “There are many known actionable mutations within NSCLC, and alterations in EGFR are amongst the most common and challenging to treat. Identifying patients whose advanced NSCLC is driven by genetic mutations and providing targeted-first line treatments, such as the combination of amivantamab and lazertinib, may help address this area of particularly high unmet medical need.” 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).1 Toxicity was largely manageable with dose interruptions and reductions, along with supportive care measures commonly used in the treatment of patients with NSCLC. The most common Grade 3 or higher treatment-related AEs were rash and paronychia.1 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.1 The rate of discontinuation of all study treatments due to treatment-related AEs for the amivantamab combination was 10 percent. The rate of interstitial lung disease (including pneumonitis) was less than three percent in both arms.1 “Amivantamab is the first fully-human bispecific antibody that targets two major oncogenic driver pathways and, when combined with lazertinib, we believe, may lead to a more complete response against the tumour,” said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. “The prolonged duration of progression-free survival and favourable trend in overall survival observed in the MARIPOSA study show the potential of amivantamab in combination with lazertinib to transform first-line treatment in EGFR-mutated NSCLC.” Amivantamab is a bispecific antibody targeting EGFR and MET with immune cell-directing activity, and in the MARIPOSA study, was combined with lazertinib, an oral third-generation EGFR tyrosine kinase inhibitor (TKI), to treat patients with locally advanced or metastatic EGFR-mutated NSCLC.1,2,3,4,5,6,7 In the study, 1,074 patients were randomised to receive treatment with amivantamab plus lazertinib, osimertinib alone or lazertinib alone.1 The primary endpoint was PFS following treatment with amivantamab plus lazertinib compared to osimertinib as assessed by blinded independent central review (BICR) according to RECIST v1.1.1‡ Secondary endpoints included OS, objective response rate (ORR), DOR and intracranial PFS.1 Results from MARIPOSA will support future planned health authority submissions. #ENDS# 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 substitution mutations.1 The primary endpoint of the study is PFS (using RECIST v1.1 guidelines) as assessed by blinded independent central review.1 Secondary endpoints include OS, ORR, DOR, second progression free survival (PFS2) and intracranial PFS.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 EGFR exon 20 insertion mutations, after failure of platinum-based therapy.2 Amivantamab is the first approved treatment in the European Union specifically targeting EGFR exon 20 insertion mutations for NSCLC.2 In October 2023, a marketing authorisation application was submitted to the European Medicines Agency seeking approval for the combination of amivantamab in combination with chemotherapy (carboplatin-pemetrexed) for the first-line treatment of patients with NSCLC with EGFR exon 20 insertion mutations.8 In addition to the Phase 3 MARIPOSA study, amivantamab is being studied in multiple clinical trials in NSCLC, including: The Phase 3 MARIPOSA-2 (NCT04988295) study assessing the efficacy of amivantamab (with or without lazertinib) and carboplatin-pemetrexed versus carboplatin-pemetrexed in patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC after disease progression on or after osimertinib. Topline data for this randomised Phase 3 study demonstrated statistically significant and clinically meaningful improvement in PFS in patients receiving amivantamab plus chemotherapy with and without lazertinib versus chemotherapy.1,9,10The Phase 3 PAPILLON (NCT04538664) study assessing amivantamab in combination with carboplatin-pemetrexed versus carboplatin-pemetrexed in the first-line treatment of patients with advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. Topline data for this randomised Phase 3 study demonstrated statistically significant and clinically meaningful improvement in PFS in patients receiving amivantamab versus chemotherapy.11,12The Phase 1 CHRYSALIS (NCT02609776) study evaluating amivantamab in participants with advanced NSCLC.13The 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.14The Phase 1 PALOMA (NCT04606381) study assessing the feasibility of subcutaneous (SC) administration of amivantamab based on safety and pharmacokinetics and to determine a dose, dose regimen and formulation for amivantamab SC delivery.15The Phase 2 PALOMA-2 (NCT05498428) study assessing subcutaneous amivantamab in participants with advanced or metastatic solid tumors including EGFR-mutated NSCLC.16The Phase 3 PALOMA-3 (NCT05388669) study assessing lazertinib with subcutaneous amivantamab compared to intravenous amivantamab in participants with EGFR-mutated advanced or metastatic NSCLC.17The Phase 1/2 METalmark (NCT05488314) study assessing amivantamab and capmatinib combination therapy in locally advanced or metastatic NSCLC.18The 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.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.2 ▼ In line with EMA regulations for new medicines and those given conditional approval, amivantamab is subject to additional monitoring. About LazertinibLazertinib 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 in The Journal of Clinical Oncology in 2023.7 In 2018, Janssen Biotech, Inc., entered into a license and collaboration agreement with Yuhan Corporation for the development of lazertinib. About Non-Small Cell Lung CancerIn Europe, it is estimated that 477,534 patients were diagnosed with lung cancer in 2020, with around 85 percent diagnosed with NSCLC.20,21 Lung cancer is Europe’s biggest cancer killer, with more deaths than breast cancer and prostate cancer combined.21 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.22 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.23 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.24,25,26,27 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.28 The five-year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR TKIs is less than 20 percent.29,30 Patients with EGFR ex19del or L858R mutations have a real-world five-year OS of 19 percent.31About the Janssen Pharmaceutical Companies of Johnson & JohnsonAt 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 at www.janssen.com/emea. Follow us at www.linkedin.com/janssenEMEA for our latest news. Janssen Pharmaceutica NV, Janssen-Cilag GmbH, and Janssen Research & Development, LLC are Johnson & Johnson companies. Cautions Concerning Forward-Looking StatementsThis 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 Research and Development, LLC, Janssen Biotech, Inc., Jannsen-Cilag GmbH, 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 the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. # # # *Dr. Cho has served as a consultant to Janssen; he has not been paid for any media work. †The ECOG Performance Status Scale is a score that estimates a patient’s ability to perform certain activities of daily living without the help of others. ‡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. 1 Cho 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, 2023.2 European Medicines Agency. Amivantamab Summary of Product Characteristics. January 2023. Available at: Rybrevant, INN-amivantamab (europa.eu). Accessed: October 2023.3 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):114-126.4 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):1194-1209.5 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):2044-2056.6 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):3942-3953.7 Cho, BC, et al. (2023). Lazertinib versus gefitinib as first-line treatment in patients with EGFR-mutated advanced non-small-cell lung cancer: Results From LASER301. J Clin Oncol. JCO2300515. Advance online publication. Available at: https://c212.net/c/link/?t=0&l=en&o=3957815-1&h=1674621843&u=https://doi.org/10.1200/JCO.23.00515&a=https://doi.org/10.1200/JCO.23.00515. Accessed October 20238 Janssen EMA. Press Release. Available at: https://www.janssen.com/emea/sites/www_janssen_com_emea/files/papillon_ema_filing_release.pdf Accessed: October 2023.9 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://clinicaltrials.gov/ct2/show/NCT04988295. Accessed October 2023.10 Jnj.com. Press Release. Available at: https://www.jnj.com/phase-3-mariposa-2-study-meets-dual-primary-endpoint-resulting-in-statistically-significant-and-clinically-meaningful-improvement-in-progression-free-survival-for-rybrevant-amivantamab-vmjw-plus-chemotherapy-with-and-without-lazertinib-versus-chemotherapy-alone-in-patients-with-egfr-mutated-non-small-cell-lung-cancer-after-disease-progression-on-osimertinib. Accessed October 202311 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 byEpidermal Growth Factor Receptor (EGFR) Exon 20 Insertions (PAPILLON). Available at: https://clinicaltrials.gov/ct2/show/NCT04538664. Accessed October 2023.12 Zhou C, et al. Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. The New England Journal of Medicine. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa2306441. Accessed October 2023.13 ClinicalTrials.gov. A Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer (CHRYSALIS). Available at: https://clinicaltrials.gov/ct2/show/NCT02609776. Accessed October 2023.14 ClinicalTrials.gov. A Study of Lazertinib as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer (CHRYSALIS-2). Available at: https://clinicaltrials.gov/ct2/show/NCT04077463. Accessed October 2023.15 ClinicalTrials.gov. A Study of Amivantamab Subcutaneous (SC) Administration for the Treatment of Advanced Solid Malignancies (PALOMA). Available at: https://clinicaltrials.gov/ct2/show/NCT04606381. Accessed October 2023.16 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). Available at: https://clinicaltrials.gov/ct2/show/NCT05498428. Accessed October 2023.17 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). Available at: https://clinicaltrials.gov/ct2/show/NCT05388669. Accessed October 2023.18 ClinicalTrials.gov. A Study of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer (METalmark). Available at: https://clinicaltrials.gov/ct2/show/NCT05488314. Accessed October 2023.19 ClinicalTrials.gov. Premedication to Reduce Amivantamab Associated Infusion Related Reactions (SKIPPirr). Available at: https://classic.clinicaltrials.gov/ct2/show/NCT05663866. Accessed October 2023.20 Globocan 2020. Estimated number of incident cases deaths in 2020, Europe, both sexes, all ages. Available at: www.gco.iarc.fr. Accessed October 2023.21 Zappa C et al. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res 2016;5(3): 288–300.22 Oxnard JR, et al. Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions. J Thorac Oncol. 2013 Feb;8(2):179-84. doi: 10.1097/JTO.0b013e3182779d18.23 Bauml JM, et al. Underdiagnosis of EGFR Exon 20 Insertion Mutation Variants: Estimates from NGS-based Real World Datasets. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore.24 Pennell 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. 37:97-104.25 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; January 29, 2021; Singapore.26 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):78985-78993.27 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):2892-2911.28 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 October 2023.29 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.30 Lin JJ, et al. Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs. J Thorac Oncol. 2016 Apr;11(4):556-65.31 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. CP-417579 October 2023 CONTACT: Media Contacts:
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