Lazertinib

Johnson & Johnson (J&J) has announced that its chemotherapy-free combination significantly extended overall survival (OS) compared to standard of care in a subset of non-small cell lung cancer (NSCLC) patients. The phase 3 MARIPOSA study has been evaluating Rybrevant (amivantamab), an EGFR-MET bispecific antibody, plus Lazcluze (lazertinib), a third-generation EGFR tyrosine kinase inhibitor (TKI), against AstraZeneca’s own third-generation EGFR-TKI Tagrisso (osimertinib) as a first-line treatment for locally advanced or metastatic NSCLC in patients with EGFR exon 19 deletions or exon 21 L858R substitution mutations. J&J previously reported in 2023 that the study met its primary endpoint, with the combination demonstrating a statistically significant and clinically meaningful improvement in progression-free (PFS) compared to Tagrisso. New data presented at this year’s European Lung Cancer Congress showed that, at a median follow-up of 37.8 months, median OS for Rybrevant plus Lazcluze had not yet been reached, while median OS for Tagrisso-treated patients was 36.7 months. Among patients receiving J&J’s combination, 56% were alive at three and a half years compared to 44% of patients on Tagrisso, with projections suggesting Rybrevant plus Lazcluze could extend median OS by at least 12 months compared to AZ’s drug. The combination also prolonged multiple secondary endpoints versus Tagrisso, including intracranial PFSl, intracranial duration of response and intracranial overall response rate. NSCLC accounts for up to 85% of all lung cancer cases, and alterations in EGFR are among the most common driver mutations in patients with this form of the disease. “Right now, only 20% of patients with EGFR-positive NSCLC survive beyond five years,” explained Joshua Bauml, vice president, Lung Cancer Disease Area Stronghold Leader, J&J Innovative Medicine. “These MARIPOSA results suggest that Rybrevant plus Lazcluze can change this dire statistic that has been stagnant for far too long.” “This regimen isn’t just extending survival, it’s offering hope. By using Rybrevant plus Lazcluze first, we’re delaying the need for chemotherapy and giving patients and their families more time,” Bauml added. The announcement comes just three weeks after Lazcluze plus Rybrevant was approved by the Medicines and Healthcare products Regulatory Agency (MHRA) for EGFR-mutated NSCLC. The combination has also already been approved in the US, EU and other markets for this indication. J&J said the latest OS results will be shared with health authorities globally.

Median overall survival not yet reached with projected improvement of more than one year versus osimertinib RARITAN, NJ, USA I March 26, 2025 I Johnson & Johnson (NYSE: JNJ ) today announced results for the gold standard endpoint in cancer treatment of overall survival (OS) from the Phase 3 MARIPOSA study. Head-to-head comparison data versus osimertinib showed RYBREVANT ® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) significantly extended OS in the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor ( EGFR ) exon 19 deletions (ex19del) or L858R substitution mutations. Median OS is projected to exceed one year beyond the median of three years observed with osimertinib and has not yet been reached. This is the first and only study to show a statistically significant and clinically meaningful OS improvement over osimertinib. New compelling data were presented during a proffered paper session at the 2025 European Lung Cancer Congress (ELCC) (Abstract #4O). 1 “The survival curve tells a clear story. RYBREVANT plus LAZCLUZE helps patients live longer, and the benefit keeps growing over time,” said trial investigator Professor Nicolas Girard*, M.D., Ph.D., Head of Medical Oncology, Institut Curie, and Professor of Thoracic Oncology and Respiratory Medicine at the Paris-Saclay University, France. “We see the gap between the survival curves continue to widen, which is exactly what we want to see in lung cancer treatment to improve outcomes for patients. These results reinforce that we are entering a new era for EGFR -mutated non-small cell lung cancer; with this evidence in hand, we need to ensure every patient gets the most effective treatment in the first line for the best possible chance at longer survival.” Unlike progression-free survival (PFS), which tracks the time a treatment keeps a patient’s cancer from progressing, OS helps patients understand the impact therapy could have on the ability to live longer from the start of treatment. Extending life expectancy is the most meaningful indicator of a treatment’s impact. At a median follow-up of 37.8 months, patients treated with the chemotherapy-free regimen of first-line RYBREVANT ® plus LAZCLUZE™ had a significantly longer OS compared to those receiving osimertinib (hazard ratio [HR], 0.75; 95 percent confidence interval [CI], 0.61-0.92; nominal P<0.005). Median OS for RYBREVANT ® plus LAZCLUZE™ has not yet been reached, indicating that survival benefits continue to extend beyond the measured follow-up period (not reached [NR]; 95 percent CI, 42.9-NR). Comparatively, median OS for osimertinib-treated patients was 36.7 months (95 percent CI, 33.4-41.0) and consistent with prior studies with osimertinib. Fifty-six percent of patients treated with RYBREVANT ® and LAZCLUZE™ were alive at three and a half years compared to 44 percent of patients on osimertinib. Projections based on survival data suggest RYBREVANT ® plus LAZCLUZE™ could extend median OS by at least 12 months compared to osimertinib. 1 The RYBREVANT ® combination also prolonged multiple secondary endpoints vs osimertinib, including intracranial PFS, intracranial duration of response (DOR) and intracranial overall response rate (ORR). Notably, RYBREVANT ® plus LAZCLUZE™ prolonged time to symptomatic progression (TTSP) – the time from treatment randomization to the onset of lung cancer symptoms – by more than 14 months compared to osimertinib (43.6 months vs 29.3 months; HR, 0.69; 95 percent CI, 0.57–0.83; nominal P<0.001). This is a key patient-centered measure, highlighting how long quality of life can be preserved before lung cancer symptoms emerge. 1 “Right now, only twenty percent of patients with EGFR- positive NSCLC survive beyond five years. These MARIPOSA results suggest that RYBREVANT plus LAZCLUZE can change this dire statistic that has been stagnant for far too long,” said Joshua Bauml, M.D., Vice President, Lung Cancer Disease Area Stronghold Leader, Johnson & Johnson Innovative Medicine. “This regimen isn’t just extending survival, it’s offering hope. By using RYBREVANT plus LAZCLUZE first, we’re delaying the need for chemotherapy and giving patients and their families more time.” The safety profile of RYBREVANT ® plus LAZCLUZE™ was consistent with the primary analysis, with adverse event (AE) rates comparable to other RYBREVANT ® regimens. No new safety signals were identified with the additional longer-term follow-up. Most AEs occurred early during RYBREVANT ® and LAZCLUZE™ treatment. 1 RYBREVANT ® research findings suggest that implementing prophylactic measures during the first four months of RYBREVANT ® and LAZCLUZE™ treatment may significantly reduce the risk of skin reactions, infusion-related reactions and venous thromboembolic events. 2,3,4 The MARIPOSA study met its primary endpoint in October 2023, showing a statistically significant and clinically meaningful improvement in PFS compared to osimertinib. RYBREVANT ® plus LAZCLUZE™ is approved in the United States, Europe and other markets around the world for patients with first-line EGFR -mutated NSCLC. These OS results will be shared with health authorities globally. 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 ex19del or substitution mutations. The primary endpoint of the study is PFS (using RECIST v1.1 guidelines**) as assessed by BICR. Secondary endpoints include OS, ORR, DOR, PFS2 and intracranial PFS. 5 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 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. 6 RYBREVANT ® is approved in the U.S. , Europe and other markets around the world 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. RYBREVANT ® is approved in the U.S., Europe and other markets around the world in combination with LAZCLUZE™ (lazertinib) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test. RYBREVANT ® is approved in the U.S. , Europe and other markets around the world in combination with chemotherapy (carboplatin-pemetrexed) for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, whose disease has progressed on or after treatment with an EGFR TKI. In February 2025, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended the approval of SC amivantamab and LAZCLUZE™ in Europe for the first-line treatment of adult patients with advanced NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, and as a monotherapy for the treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy. 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 the Phase 3 MARIPOSA Study, 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™ (marketed as LECLAZA in South 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. 21 About Non-Small Cell Lung Cancer Worldwide, lung cancer is one of the most common cancers, with NSCLC making up 80 to 85 percent of all lung cancer cases. 22,23 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. 24 Among the most common driver mutations in NSCLC are alterations in EGFR , which is a receptor tyrosine kinase controlling cell growth and division. 25 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. 22,23,26,27,28,29 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations. 30 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. 31,32 EGFR exon 20 insertion mutations are the third most prevalent activating EGFR mutation. 33 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. 34 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 http://www.innovativemedicine.jnj.com/ . Follow us at @JNJInnovMed . Janssen-Cilag International NV, Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen Global Services, LLC and Janssen-Cilag, S.A. are Johnson & Johnson companies. *Nicolas Girard, M.D., Ph.D., has served as a consultant to Johnson & Johnson; he has not been paid for any media work. **RECIST (version 1.1) refers to Response Evaluation Criteria in Solid Tumors, which is a standard way to measure how well solid tumors respond to treatment and is based on whether tumors shrink, stay the same or get bigger. †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. 1 Yang J, et al. Amivantamab Plus Lazertinib vs Osimertinib in First-line (1L) EGFR-mutant (EGFRm) Advanced NSCLC: Final Overall Survival (OS) from the Phase 3 MARIPOSA Study. 2025 European Lung Cancer Congress. March 26, 2025. 2 Johnson & Johnson. COCOON study meets primary endpoint demonstrating statistically significant and clinically meaningful reduction in dermatologic reactions with easy-to-use prophylactic regimen for patients with EGFR-mutated NSCLC. January 14, 2025. Accessed February 13, 2025. 3 Spira AI, et al. J Thorac Oncol. 2025. In press. 4 Leighl N, et al. J Clin Oncol. 2024;42(30):3593-3605. 5 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 March 2025. 6 RYBREVANT® Prescribing Information. Horsham, PA: Janssen Biotech, Inc. 7 Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2025 © 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 March 2025. 8 ClinicalTrials.gov. A Study of Amivantamab and LAZCLUZE™ 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 March 2025. 9 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 March 2025. 10 ClinicalTrials.gov. A Study of LAZCLUZE™ 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 March 2025. 11 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 March 2025. 12 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 March 2025. 13 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 March 2025. 14 ClinicalTrials.gov. A Study of LAZCLUZE™ 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 March 2025. 15 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 March 2025. 16 ClinicalTrials.gov. A Study of Combination Therapy With Amivantamab and Docetaxel in Participants With Metastatic Non-small Cell Lung Cancer (swalloWTail). https://www.clinicaltrials.gov/study/NCT06532032. Accessed March 2025. 17 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. Accessed March 2025. 18 ClinicalTrials.gov. Premedication to Reduce Amivantamab Associated Infusion Related Reactions (SKIPPirr). https://classic.clinicaltrials.gov/ct2/show/NCT05663866. Accessed March 2025. 19 ClinicalTrials.gov. A Study of Amivantamab in Combination With Lazertinib, or Amivantamab in Combination With Platinum-Based Chemotherapy, for Common Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) (COPERNICUS). https://www.clinicaltrials.gov/study/NCT06667076. Accessed March 2025. 20 ClinicalTrials.gov. Enhanced Dermatological Care to Reduce Rash and Paronychia in Epidermal Growth Factor Receptor (EGRF)-Mutated Non-Small Cell Lung Cancer (NSCLC) Treated First-line With Amivantamab Plus Lazertinib (COCOON). https://www.clinicaltrials.gov/study/NCT06120140. Accessed March 2025. 21 Cho BC, et al. Lazertinib versus gefitinib as first-line treatment in patients with EGFR-mutated advanced non-small-cell lung cancer: Results From LASER301. J Clin Oncol. 2023;41(26):4208-4217. 22 The World Health Organization. Cancer. https://www.who.int/news-room/fact-sheets/detail/cancer. Accessed March 2025. 23 American Cancer Society. What is Lung Cancer? https://www.cancer.org/content/cancer/en/cancer/lung-cancer/about/what-is.html. Accessed March 2025. 24 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: 10.10 25 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. 26 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. 27 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. 28 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. 29 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. 30 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 March 2025. 31 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. 32 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. 33 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. 34 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. 35 LAZCLUZE™ Prescribing Information. Horsham, PA: Janssen Biotech, Inc. SOURCE: Johnson & Johnson