EGFR positive non-small cell lung cancer

The 8 mg pre-medication regimen showed an infusion-related reaction rate of 22.5 percent with intravenous amivantamab, a three-fold reduction from 67.4 percent historically seen with standard IRR management 1 ,2 BEERSE, BELGIUM, Sept. 10, 2024 (GLOBE NEWSWIRE) -- Janssen-Cilag International NV, a Johnson & Johnson company, today announced results from the open-label Phase 2 SKIPPirr study, which evaluated additional prophylactic strategies to reduce the incidence of infusion-related reactions (IRRs) with intravenous (IV) RYBREVANT ® ▼ (amivantamab) in patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor ( EGFR ) exon 19 deletions (ex19del) or L858R substitution mutations. 1 Many monoclonal antibodies are associated with increased rates of IRRs and IRRs with amivantamab are of special interest to the European Medicines Agency (EMA). 2 ,3 The study, which included 40 patients, showed that prophylaxis with 8 mg dexamethasone taken for two days prior to the first infusion met the primary endpoint of incidence of IRRs at Cycle 1 Day 1 (C1D1), with an all-grades IRR rate for IV amivantamab of 22.5 percent. 1 There were three additional arms to the study exploring different prophylactic regimens: group 1 (dexamethasone 4 mg, one dose taken orally twice daily on the day before treatment ), group 3 (montelukast 10 mg, five doses starting four days before treatment and continuing through the day of treatment) and group 4 (methotrexate 25 mg subcutaneous injection, administered between days 7 and 3 before treatment). 1 Group 1, 3 and 4 were stopped for futility. 1 The results of group 2 (dexamethasone 8 mg, taken for two days prior to infusion) showed a three-fold reduction in the incidence of IRRs compared to standard management of IRRs with IV amivantamab, where historic data has observed an all-grades incidence rate of 67.4 percent. 1 , 2 Data were presented as a mini-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 #1785). 1 “These data offer important insights that may help improve the patient experience with intravenous amivantamab treatment,” said Gilberto Lopes, M.D., Associate Director of Global Oncology at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, and presenting author.* “This study shows us that an easily accessible approach of an increased dose regimen of dexamethasone as a pre-treatment prophylaxis can potentially help lower IRRs. It is encouraging to see a three-fold decrease in IRRs, when comparing the rates in SKIPPirr to historical data.”  “At Johnson & Johnson, we are deeply committed to advancing patient care and improving the treatment experience for those with EGFR-mutated non-small cell lung cancer,” said Henar Hevia, Ph.D., Senior Director, EMEA Therapeutic Area Lead, Oncology, Johnson & Johnson Innovative Medicine. “The findings of this study show the value of comprehensive management strategies, including prophylactic interventions like dexamethasone, in reducing IRRs and optimising treatment experience with intravenous amivantamab and oral lazertinib.” In the study, patients received an at-home regimen of oral dexamethasone, taking an 8 mg dose twice daily on the two prior days and one dose one hour prior to receiving IV amivantamab, in addition to the standard prophylactic regimen. 1 The amivantamab treatment was combined with lazertinib. 1 All IRRs were Grade 1 or 2 with no patients requiring hospitalisation due to IRRs. 1 There were no Grade 3 or higher IRR events reported. 1 The safety pro amivantamab and lazertinib with prophylactic dexamethasone at the initiation of treatment was otherwise consistent with previous studies. 1 The most common IRR-related symptoms observed in the study were nausea (8 percent), dyspnea (5 percent) and hypotension (5 percent). 1 “Reducing the risk of IRRs is a critical aspect of improving the overall treatment experience for patients receiving intravenous amivantamab and oral lazertinib,” said Mark Wildgust, Ph.D., Vice President of Oncology Global Medical Affairs, Johnson & Johnson Innovative Medicine. “By incorporating an additional treatment regimen of prophylactic oral dexamethasone we can help mitigate this risk, with the goal of allowing patients to continue their therapy with fewer interruptions.”  Additional studies are ongoing to evaluate prophylactic strategies to reduce IRRs for patients receiving IV amivantamab. About the SKIPPirr Study SKIPPirr ( NCT05663866 ) is a Phase 2 study evaluating amivantamab in combination with lazertinib in patients with EGFR -mutated (Ex19del or L858R) advanced NSCLC after disease progression on osimertinib and platinum-based chemotherapy. 1 ,4 All patients received oral lazertinib and IV amivantamab. 1 The study used a Simon’s 2-stage design to evaluate different preventive treatments across four groups. 1 The first group received dexamethasone (4 mg) orally, taken twice daily on the day before treatment, for a total of two doses. 1 The second group was given a higher dose of dexamethasone (8 mg), taken orally twice daily on the two days leading up to treatment and the morning of infusion (5 doses total). 1 The third group received montelukast (10 mg) orally, starting four days before treatment and continuing through the day of treatment, totaling five doses. 1 Lastly, the fourth group was treated with a single dose of methotrexate (25 mg), administered as a subcutaneous injection between days 7 and 3 before the treatment. 1 The primary endpoint of the study is incidence of IRRs at Cycle 1 Day 1. 1 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. 5 ,6,7,8 The European Commission (EC) has granted marketing authorisation of amivantamab in the following indications: 9 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 combination 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 tyrosine kinase inhibitor (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. 10 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. 11 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 . 9 ▼ 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. 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 all people with advanced NSCLC and EGFR mutations treated with EGFR tyrosine kinase inhibitors (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 . Follow us at . Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen-Cilag, S.A. and Janssen-Cilag International NV 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 materialise, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen-Cilag, S.A. and 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 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 , or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen-Cilag, S.A. and 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. # # # *Dr. Gilberto Lopes has served as a consultant to Janssen-Cilag International NV; he has not been paid for any media work. References: 1 Lopes G, et al. Preventing Infusion-related Reactions with Intravenous Amivantamab: Primary Results From SKIPPirr, a Phase 2 Study. Oral Presentation, IASLC WCLC 2024. September 10, 2024. 2 Park K, Sabari JK, Haura EB, et al. Management of infusion-related reactions (IRRs) in patients receiving amivantamab in the CHRYSALIS study. Lung Cancer. 2023;178:166-171. 3 Barroso A, et al. Management of infusion-related reactions in cancer therapy: strategies and challenges. ESMO Open. 2024;9(3):102922. 4 ClinicalTrials.gov. Premedication to Reduce Amivantamab Associated Infusion Related Reactions (SKIPPirr). Available at: Accessed: September 2024. 5 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. 6 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. 7 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. 8 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. 9 European Medicines Agency. Amivantamab Summary of Product Characteristics. July 2024. Available at: Accessed: September 2024. 10 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. . Accessed: September 2024. 11 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: Accessed: September 2024. 12 Global Cancer Observatory. Cancer Today. Available at: . 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: 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 Apr;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-473649 September 2024 FOR EUROPEAN MEDICAL AND PHARMACEUTICAL TRADE MEDIA ONLY CONTACT: Media contact: Zayn Qureshi zqureshi@its.jnj.com +44 7760 334 666 Investor contact: Raychel Kruper investor-relations@its.jnj.com

RIDGEFIELD, Conn., Aug. 27, 2024 /PRNewswire/ -- Data from the Phase Ib Beamion LUNG-1 trial selected for late-breaking oral presentation in the Presidential Symposium at WCLC on Monday, September 9. The U.S. FDA and China's CDE have granted zongertinib Breakthrough Therapy Designation for patients with HER2-mutated NSCLC and who have received prior systemic therapy. Phase I trial data of a novel DLL3-targeting T-Cell Engager, which has already secured FDA Fast Track as well as FDA and EMA Orphan Drug Designations, will also be presented. At the IASLC 2024 World Conference on Lung Cancer (WCLC) Boehringer Ingelheim will present encouraging data from across its oncology pipeline, illustrating its aspiration to transform the lives of people with cancer by delivering meaningful advances. Carinne Brouillon, Head of Human Pharma at Boehringer said: "Every year, about 40,000 people worldwide are diagnosed with non-small cell lung cancer (NSCLC) with a HER2 mutation.i While targeted therapy is available for some cancers driven by HER2, people living with HER2-mutated NSCLC have few options. We are proud to be sharing new data evaluating our investigational zongertinib in this hard-to-treat setting. Our strong oncology pipeline underscores our strategic approach in advancing novel targeted treatments and cancer cell-directed therapies that have a potential to transform lives for generations of patients." Late-breaking results from the Beamion LUNG-1 trial, which is a Phase Ia/b trial evaluating the safety and efficacy of zongertinib (BI 1810631), a HER2-specific tyrosine kinase inhibitor (TKI), will be presented at WCLC. This includes new data from a primary analysis of the first Cohort of Phase Ib in pre-treated patients with HER2m+ NSCLC to be presented in a Presidential Symposium on Monday, September 9, from 8:30AM - 10:00AM PDT (Location: Plenary Hall) and featured in the official WCLC Press Program. Highlighting the potential of zongertinib, the investigational oral therapy was recently granted Breakthrough Therapy Designation by the U.S. FDA and China's CDE for the treatment of adult patients with advanced, unresectable or metastatic NSCLC whose tumors have activating HER2 mutations, and who have received a prior systemic therapy. Investigating the potential of DLL3 targeted immunotherapy to transform the treatment of neuroendocrine carcinomas Exploring the promise of DLL3-targeted immunotherapy in transforming the treatment of neuroendocrine carcinomas, Boehringer will present data from the Phase I trial of its novel DLL3-targeting T-Cell Engager, BI 764532 in an Oral Presentation on Monday, September 9, from 2:22 PM-2:32 PM PDT (Location: 20A). This investigational treatment, which has been granted FDA Fast Track as well as FDA and EMA Orphan Drug Designations, is currently being evaluated in patients with large-cell neuroendocrine carcinoma of the lung (LCNEC-L), small cell lung cancer (SCLC) and extrapulmonary neuroendocrine cancer (epNEC). BI 764532 is designed to redirect T-cells to target tumors that express the DLL3 protein. In addition to the five abstracts to be presented at WCLC, Boehringer will also host a symposium titled "Emerging Therapies in Clinical Practice: What are the Patient Perspectives on the Future of Lung Cancer Treatment?" on Saturday, September 7, from 3:45PM to 4:45PM PDT (Location: 30DE). At Boehringer, cancer care is personal, which is why this event will explore patient viewpoints and expectations regarding the evolving landscape of lung cancer therapy. Data from Boehringer's oncology pipeline to be presented at WCLC: About non-small cell lung cancer (NSCLC) Lung cancer claims more lives than any other cancer type and the incidence is set to increase to over 3 million cases worldwide by 2040.ii NSCLC is the most common type of lung cancer.iii The condition is often diagnosed at a late stage,iv and fewer than 3 in 10 patients are alive five years after diagnosis.v People living with advanced NSCLC can experience a detrimental physical, psychological, and emotional impact on their daily lives. There remains a high unmet need for additional treatment options for people living with advanced NSCLC. Around 4.7% of lung cancers are driven by HER2 mutations (or gene alterations).i,vi About zongertinib Zongertinib (also known as BI 1810631) is an investigational oral HER2-specific tyrosine kinase inhibitor (TKI) that is highly selective and being developed as a potential treatment for non-small cell lung cancer (NSCLC). Zongertinib was granted FDA Fast Track Designation in 2023, then in 2024 it was granted Breakthrough Therapy Designation by the U.S. FDA and China CDE for the treatment of adult patients with advanced NSCLC whose tumors have activating HER2 mutations, and who have received a prior systemic therapy. HER2 is a member of the ErbB family of receptor tyrosine kinases (enzymes that act like chemical messengers). Mutations in HER2 can lead to overexpression and overactivation, which can in turn result in uncontrolled cell production, inhibition of cell death and promotion of tumor growth and spread. Read more here. About BI 764532 BI 764532 is an investigational DLL3/CD3 IgG-like T-Cell Engager under development as a potential new targeted immunotherapy for patients with large-cell neuroendocrine carcinoma of the lung (LCNEC-L), small cell lung cancer (SCLC) & extrapulmonary neuroendocrine cancer (epNEC). The therapy is designed to directly redirect T-cells, potentially resulting in the selective killing of tumor cells by the body's own immune system. Pre-clinical in-vivo data suggests administration of DLL3/CD3 bispecific T-cell engager (ITE) monotherapy induces T-cell infiltration into tumor tissues, transforming a non-inflamed (cold) tumor microenvironment into an inflamed (hot) state. This process triggers tumor cell apoptosis, resulting in significant tumor regression. BI 764532 has been granted FDA Fast Track as well as FDA and EMA Orphan Drug Designations. Read more here. About brigimadlin Brigimadlin (also known as BI 907828) is an investigational oral MDM2-p53 antagonist being developed as a potential treatment for certain types of cancer. The small molecule compound may inhibit the interaction between MDM2 and p53, restoring p53 wild type function. Inactivation of the tumor suppressor protein p53 is a central mechanism by which cancer cells drive tumor growth. Increased levels of the protein MDM2, a key negative regulator of p53, is a well-characterized inactivation mechanism, seen in about 5-7% of all cancer cases. About Boehringer Ingelheim in Oncology We have a clear aspiration – to transform the lives of people with cancer by delivering meaningful advances, with the ultimate goal of curing a range of cancers. Boehringer Ingelheim's generational commitment to driving scientific innovation is reflected by the company's robust pipeline of cancer cell-directed and immuno-oncology investigational therapies, as well as the smart combination of these approaches. Boehringer's ambition in oncology is to take a diligent and broad approach, creating a collaborative research network to tap into a diversity of minds, which is vital in addressing some of the most challenging, but potentially most impactful, areas of cancer research. Simply put, for Boehringer Ingelheim, cancer care is personal, today and for generations. Read more here. About Boehringer Ingelheim Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry's top investors in Research and Development, the company focuses on developing innovative therapies in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. More than 53,500 employees serve over 130 markets to build a healthier, more sustainable, and equitable tomorrow. Lean more at boehringer-ingelheim.com/us. i Chia, P. et al. Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors. Clinical Epidemiology. . ii International Agency for Research on Cancer – World Health Organization. Rates of trachea, bronchus and lung cancer. Available at: (Accessed August 2024). iii Zappa C & Mousa Non-small cell lung cancer: current treatment and future advances, Transl Lung Cancer Res. 2016 Jun; 5(3): 288–300. iv Polanco D et al. Prognostic value of symptoms at lung cancer diagnosis: a three-year observational study. J Thorac Dis 2021;13:1485–1494 v National Cancer Institute Surveillance, Epidemiology, and End Results (SEER). (Accessed: August 2024). vi Arcila, M. E. et al. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin. cancer Res. an Off. J. Am. Assoc. Cancer Res. 18, 4910–4918 (2012). MPR-US-103284 8/24 SOURCE Boehringer Ingelheim

RYBREVANT ® plus LAZCLUZE™ is the first and only chemotherapy-free regimen showing superior progression-free survival versus osimertinib Following Priority Review, approval is based on Phase 3 MARIPOSA results showing RYBREVANT ® plus LAZCLUZE™ reduced the risk of disease progression or death by 30 percent versus osimertinib, with a nine-month-longer median duration of response RARITAN, NJ, USA I August 20, 2024 I Johnson & Johnson (NYSE: JNJ) announced today that the U.S. Food and Drug Administration (FDA) approved RYBREVANT ® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test. 1,2 With this milestone, RYBREVANT ® plus LAZCLUZE™ becomes the first and only multitargeted, chemotherapy-free combination regimen with demonstrated superiority versus osimertinib approved for the first-line treatment of patients with EGFR-mutated NSCLC. 1,2 RYBREVANT ® is an EGFR- and MET * -directed bispecific antibody that engages the immune system, and LAZCLUZE™ is a highly selective, brain-penetrant, third-generation oral EGFR TKI ** . RYBREVANT ® plus LAZCLUZE ™ is the only multitargeted regimen targeting both the common EGFR mutations directly. 1,2 “This approval is a crucial development for patients with EGFR-mutated NSCLC, who have faced significant unmet needs for far too long,” said Jill Feldman † , lung cancer survivor and co-founder of the EGFR Resisters, a patient advocacy group. “Having witnessed firsthand the remarkable evolution in lung cancer treatment, this profoundly important milestone brings a novel therapeutic approach to patients and their families. I’m thrilled that more patients can now experience the progression-free survival benefits seen in the MARIPOSA study.” Lung cancer is the leading cause of cancer mortality worldwide, resulting in 1.8 million deaths each year, with NSCLC accounting for 80 to 85 percent of all cases. 3,4 Of patients with EGFR-mutated NSCLC, between 25 and 39 percent never receive second-line therapy, due to disease progression and lack of treatment options. 5,6,7 The five-year survival rate is less than 20 percent for all people with advanced EGFR-mutated NSCLC treated with current standard of care TKI monotherapy. 8,9 Acquired resistance mechanisms after TKI monotherapy makes subsequent treatment more difficult. 8,9 “The unique combination of RYBREVANT and LAZCLUZE demonstrated superior efficacy in the first-line treatment of certain patients with EGFR-mutated advanced NSCLC as shown with the MARIPOSA study,” said Alexander Spira ‡ , M.D., Ph.D., FACP, Director, Virginia Cancer Specialists Research Institute, and study investigator. “Patients will now have the option of a potential new first-line standard of care with significant clinical benefits over osimertinib. This first-line therapy uses a targeted approach aiming to achieve the best possible patient outcomes while reserving chemotherapy for later stages of treatment when resistance becomes more complex.” The FDA approval is based on positive results from the Phase 3 MARIPOSA study, which showed RYBREVANT ® plus LAZCLUZE™ reduced the risk of disease progression or death by 30 percent compared to osimertinib (median progression-free survival [PFS]: 23.7 months versus 16.6 months) in the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations. 1,2 The median duration of response (DOR) was nine months longer with RYBREVANT ® plus LAZCLUZE™ versus osimertinib (25.8 months versus 16.7 months), a secondary endpoint of the study. “Building on more than three decades of oncology innovation, we are uniquely positioned to build best-in-class treatments where survival rates have remained stagnant for years,” said Jennifer Taubert, Executive Vice President, Worldwide Chairman, Innovative Medicine, Johnson & Johnson. “RYBREVANT plus LAZCLUZE establishes a new benchmark in the advanced first-line setting, and we look forward to bringing this new chemotherapy-free treatment regimen to patients.” “Johnson & Johnson is deeply committed to setting new standards of care for people living with some of the most devastating and complex diseases of our time,” said John Reed, M.D., Ph.D., Executive Vice President, Innovative Medicine, R&D, Johnson & Johnson. “Today’s FDA approval of chemotherapy-free RYBREVANT plus LAZCLUZE in the first line is an incredible step towards our goal of altering the trajectory of lung cancer and reducing the impact of the world’s leading cause of cancer mortality.” The safety profile of RYBREVANT ® plus LAZCLUZE™ was consistent with the profiles of the individual treatments. Venous thromboembolic events (VTE) were observed with the combination. Adverse event (AE) rates were consistent in this arm as compared to other RYBREVANT ® regimens. MARIPOSA Publications & Presentations Results from MARIPOSA were first presented at the European Society of Medical Oncology 2023 Congress and recently published in The New England Journal of Medicine . Results presented at the 2024 American Society of Clinical Oncology annual meeting and published in Annals of Oncology demonstrated the combination’s significant benefit for patients who have at least one high-risk feature, which represents 85 percent of all EGFR-mutated NSCLC cases. 10 Longer-term follow-up data from MARIPOSA will be presented at the International Association for the Study of Lung Cancer (IASLC) 2024 World Congress on Lung Cancer (WCLC) in September. Regulatory Milestones This approval marks the second new indication this year for RYBREVANT ® , following the March 1, 2024, U.S. FDA approval of RYBREVANT ® in combination with chemotherapy (carboplatin-pemetrexed) for the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, based on the Phase 3 PAPILLON study. 1 On June 17, Johnson & Johnson announced the submission of a Biologics License Application (BLA) to the U.S. FDA for a fixed combination of amivantamab and recombinant human hyaluronidase for subcutaneous administration (SC amivantamab) for all currently approved or submitted indications of intravenous (IV) RYBREVANT ® . This application is based on the Phase 3 PALOMA-3 study, with preliminary results showing a five-fold reduction in infusion-related reactions (IRR) with a five-minute administration of SC amivantamab. 11 Longer overall survival (OS), PFS and DOR were also observed with SC amivantamab. 11 On August 14, the U.S. FDA designated this application for Priority Review. About the MARIPOSA Study MARIPOSA ( NCT04487080 ), which enrolled 1,074 patients, is a randomized, Phase 3 study evaluating RYBREVANT ® in combination with LAZCLUZE™ versus osimertinib and versus LAZCLUZE™ alone in first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or substitution mutations. The primary endpoint of the study is PFS (using RECIST v1.1 guidelines) as assessed by blinded independent central review (BICR). Secondary endpoints include OS, overall response rate (ORR), DOR, second progression-free survival (PFS2) and intracranial PFS. 12 About RYBREVANT ® RYBREVANT ® (amivantamab-vmjw), a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity, is approved in the U.S. , Europe , and in other markets around the world as monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. 1 In the subcutaneous formulation, amivantamab is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE ® drug delivery technology. RYBREVANT ® is approved in the U.S. in combination with chemotherapy (carboplatin and pemetrexed) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test. In April 2024, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended the approval of RYBREVANT ® in Europe for this indication. RYBREVANT ® is approved in the U.S. in combination with LAZCLUZE™ for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, as detected by an FDA-approved test. A marketing authorization application (MAA) and type II extension of indication application were submitted to the EMA seeking approval of LAZCLUZE™ in combination with RYBREVANT ® based on the MARIPOSA study. In November 2023, Johnson & Johnson submitted a supplemental BLA to the U.S. FDA for RYBREVANT ® in combination with chemotherapy for the treatment of patients with EGFR-mutated NSCLC who progressed on or after osimertinib based on the MARIPOSA-2 study. A type II extension of indication application was also submitted to the EMA seeking approval of RYBREVANT ® for this indication. In June 2024, Johnson & Johnson submitted a BLA to the U.S. FDA for the subcutaneous formulation of RYBREVANT ® in combination with LAZCLUZE™ for all currently approved or submitted indications of intravenous (IV) RYBREVANT ® in certain patients with NSCLC. In August 2024, the U.S. FDA designated this application for Priority Review. The National Comprehensive Cancer Network ® (NCCN ® ) Clinical Practice Guidelines in Oncology (NCCN Guidelines ® ) for NSCLC # prefer next-generation sequencing-based strategies over polymerase chain reaction-based approaches for the detection of EGFR exon 20 insertion variants. The NCCN Guidelines include: In addition to MARIPOSA, RYBREVANT ® is being studied in multiple clinical trials in NSCLC, including: For more information, visit: https://www.RYBREVANT.com . About LAZCLUZE™ In 2018, Janssen Biotech, Inc., entered into a license and collaboration agreement with Yuhan Corporation for the development of LAZCLUZE™ (lazertinib, marketed as LACLAZA in Korea). LAZCLUZE™ 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 LAZCLUZE™ from the Phase 3 LASER301 study was published in The Journal of Clinical Oncology in 2023. Access to RYBREVANT ® and LAZCLUZE™️ J&J offers comprehensive access and support information and resources to assist patients in gaining access to RYBREVANT ® and LAZCLUZE™. Our patient support program, J&J withMe, is available to provide personalized support to help patients start and stay on their J&J medicines. J&J withMe offers providers help supporting their patients by verifying patients’ insurance coverage, providing information on Prior Authorization and Appeals processes and educating on reimbursement processes. Patients can connect to RYBREVANT withMe to receive cost support, regardless of insurance type, free, personalized one-on-one support from a Care Navigator, and resources and community connections. Learn more at RYBREVANTwithMe.com or by calling 833-JNJ-wMe1 (833-565-9631). ♠ About Non-Small Cell Lung Cancer (NSCLC) Lung cancer is one of the most common cancers worldwide, with NSCLC making up 80 to 85 percent of all cases. 3,4 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. 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. 23,24,25,26,27,28 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations. 29 The five-year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR tyrosine kinase inhibitors is less than 20 percent. 8,9 EGFR exon 20 insertion mutations are the third most prevalent activating EGFR mutation. 30 Patients with EGFR exon 20 insertion mutations have a real-world five-year 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. 31 Please read full Prescribing Information for RYBREVANT ® . Please read full Prescribing Information for LAZCLUZE™. 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://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine . Follow us at @JanssenUS and @JNJInnovMed . Janssen Research & Development, LLC, and Janssen Biotech, Inc., are Johnson & Johnson companies. * Mesenchymal-epithelial transition ** Tyrosine kinase inhibitor ‡ Dr. Alexander Spira has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work. § See the NCCN Guidelines for detailed recommendations, including other treatment options. ¶ The NCCN Guidelines for NSCLC provide recommendations for certain individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories. # The NCCN content does not constitute medical advice and should not be used in place of seeking professional medical advice, diagnosis or treatment by licensed practitioners. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. ♠ The patient support and resources provided by J&J withMe are not intended to provide medical advice, replace a treatment plan from the patient’s doctor or nurse, provide case management services, or serve as a reason to prescribe a J&J medicine. 1 RYBREVANT® Prescribing Information. Horsham, PA: Janssen Biotech, Inc. 2 LAZCLUZE™ Prescribing Information. Horsham, PA: Janssen Biotech, Inc. 3 The World Health Organization. Cancer. https://www-who-int.libproxy1.nus.edu.sg/news-room/fact-sheets/detail/cancer. Accessed June 2024. 4 American Cancer Society. What is Lung Cancer? https://www.cancer.org/content/cancer/en/cancer/lung-cancer/about/what-is.html. Accessed June 2024. 5 Lee JY, Mai V, Garcia M, et al. Treatment patterns and outcomes of first-line osimertinib-treated advanced EGFR mutated NSCLC patients: a real-world study [IASLC abstract EP08.02-082]. Presented at: IASLC 2022 World Lung Conference on Lung Cancer; August 6-9, 2022; Vienna, Austria. 6 Nieva J, Karia PS, Okhuoya P, 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 [ESMO abstract 1344P]. Ann Oncol. 2023;34(suppl 2):S774. 7 Girard N, Leighl NB, Ohe Y, et al. Mortality among EGFR-mutated advanced NSCLC patients after starting frontline osimertinib treatment: a real-world, US attrition analysis. Presented at: the European Lung Cancer Congress; March 29-April 1, 2023; Copenhagen, Denmark. Poster 19P. 8 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. 9 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. 10 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. May 31, 2024. 11 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 June 2024. 12 ClinicalTrials.gov. A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (MARIPOSA). https://classic.clinicaltrials.gov/ct2/show/NCT04487080. Accessed June 2024. 13 Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.1.2024© National Comprehensive Cancer Network, Inc. All rights reserved. To view the most recent and complete version of the guideline, go online to NCCN.org. Accessed June 2024. 14 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). https://classic.clinicaltrials.gov/ct2/show/study/NCT04988295. Accessed June 2024. 15 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). https://clinicaltrials.gov/ct2/show/NCT04538664. Accessed June 2024. 16 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 June 2024. 17 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 June 2024. 18 ClinicalTrials.gov. A Study of Amivantamab Subcutaneous (SC) Administration for the Treatment of Advanced Solid Malignancies (PALOMA). https://clinicaltrials.gov/study/NCT04606381. Accessed June 2024. 19 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 June 2024 20 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 June 2024. 21 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 June 2024. 22 ClinicalTrials.gov. Premedication to Reduce Amivantamab Associated Infusion Related Reactions (SKIPPirr). https://classic.clinicaltrials.gov/ct2/show/NCT05663866. Accessed June 2024. 23 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 24 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. 25 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. 26 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. 27 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. 28 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. 29 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 June 2024. 30 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. 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. SOURCE: Johnson & Johnson