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Landmark Phase 3 MARIPOSA Study Meets Primary Endpoint Resulting in Statistically Significant and Clinically Meaningful Improvement in Progression-Free Survival for RYBREVANT® (amivantamab-vmjw) plus Lazertinib Versus Osimertinib in Patients with EGFR-Mut

2023-09-28

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临床结果临床3期引进/卖出临床2期加速审批

Planned interim overall survival analysis showed a trend favoring the combination of RYBREVANT® and lazertinib compared to osimertinib*

First pivotal study to show a clinically meaningful benefit in a chemotherapy-free regimen versus osimertinib

RARITAN, NJ, USA I September 28, 2023 I The Janssen Pharmaceutical Companies of Johnson & Johnson today announced positive topline results from the Phase 3 MARIPOSA study evaluating RYBREVANT® (amivantamab-vmjw), a bispecific antibody targeting epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET), in combination with lazertinib, an oral third-generation EGFR tyrosine kinase inhibitor (TKI), versus osimertinib as first-line treatment in patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC).1

The pivotal Phase 3 MARIPOSA study met its primary endpoint with a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in patients receiving RYBREVANT® plus lazertinib compared to osimertinib. The combination of RYBREVANT® and lazertinib demonstrated a safety profile consistent with previously reported data on the combination. A planned interim overall survival (OS) analysis showed a trend favoring the combination of RYBREVANT® and lazertinib compared to osimertinib. Patients in the study will be followed for subsequent OS analyses, which will determine the statistical and clinical significance of OS.1*

"Positive topline results from the MARIPOSA study reinforce the potential of the RYBREVANT and lazertinib combination in frontline EGFR-mutated non-small cell lung cancer as a future standard of care," said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. "As a combination targeted regimen, RYBREVANT and lazertinib inhibit critical oncogenic driver pathways and activate the immune system to address disease in multiple ways."

"Patients with treatment-naïve EGFR-mutated non-small cell lung cancer have historically been treated with EGFR TKIs, but these agents invariably lead to resistance and disease progression when used as monotherapy," said Alexander Spira†, M.D., Ph.D., FACP, Director, Virginia Cancer Specialists Research Institute, and study investigator. "These promising data from MARIPOSA underscore the potential for the RYBREVANT and lazertinib regimen to advance treatment beyond TKI monotherapy."

MARIPOSA (NCT04487080), which enrolled 1,074 patients, is a randomized, open-label Phase 3 study evaluating RYBREVANT® in combination with lazertinib versus osimertinib and versus lazertinib alone in first-line treatment of patients with locally advanced or metastatic NSCLC locally advanced or metastatic NSCLC with EGFR exon 19 deletions (ex19del) or substitution mutations. The primary endpoint of the study is PFS (using RECIST v1.1 guidelines‡) as assessed by blinded independent central review. Secondary endpoints include OS, objective response rate (ORR), duration of response (DoR), intracranial PFS, PFS after first subsequent therapy (PFS2) and time to symptomatic progression.1

MARIPOSA marks the third RYBREVANT® Phase 3 study to readout this year following PAPILLON and MARIPOSA-2. Janssen plans to submit these results for presentation at an upcoming scientific congress, including additional details on select secondary endpoints.

About RYBREVANT®

RYBREVANT® (amivantamab-vmjw), a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity, received accelerated approval by the U.S. Food and Drug Administration (FDA) in May 2021 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.2 This indication is approved under accelerated approval based on ORR and DoR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. RYBREVANT® has also received approval from health authorities in Europe, as well as other markets around the world.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer§ prefer next-generation sequencing-based strategies over polymerase chain reaction-based approaches for the detection of EGFR exon 20 insertion variants, and include amivantamab-vmjw (RYBREVANT®) as a subsequent therapy option with a Category 2A recommendation for patients that have progressed on or after platinum-based chemotherapy with or without immunotherapy and have EGFR exon 20 insertion mutation-positive advanced NSCLC.3‖¶

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 Lazertinib

Lazertinib is an oral, third-generation, brain-penetrant EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild type-EGFR. An analysis of the efficacy and safety of lazertinib from the Phase 3 LASER301 (NCT04248829) study was published in The Journal of Clinical Oncology in 2023 and demonstrated lazertinib improved PFS compared to the first generation EGFR TKI gefitinib in all prespecified subgroups, including Asian patients, those with L858R mutations and those with a history of brain metastases.14 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 Cancer

Worldwide, lung cancer is one of the most common cancers, with NSCLC making up 80 to 85 percent of all lung cancer cases.15,16 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.17 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.18 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. 17,18,19,20,21,22 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.23 The five-year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR TKIs is less than 20 percent.24,25 Patients with EGFR ex19del or L858R mutations have a real-world five-year OS of 19 percent.26

Please read the full Prescribing Information for RYBREVANT®.

About the Janssen Pharmaceutical Companies of Johnson & Johnson

At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular, Metabolism & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension.

Learn more at www.janssen.com. Follow us at @JNJInnovMed and @JanssenUS. Janssen Research & Development, LLC and Janssen Biotech, Inc., are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

†Dr. Spira has served as a consultant to Janssen; 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.

§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 representations or warranties and explicitly disclaims the appropriateness or applicability of the NCCN Content to any specific patient's care or treatment.

‖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.

1 ClinicalTrials.gov. A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (MARIPOSA). Available at: https://clinicaltrials.gov/ct2/show/NCT04487080. Accessed September 2023.

2 RYBREVANT® Prescribing Information. Horsham, PA: Janssen Biotech, Inc.

3 Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2022. © National Comprehensive Cancer Network, Inc.Cancer Network, Inc. 2022. All rights reserved. Accessed September 2023. To view the most recent and complete version of the guideline, go online to NCCN.org.

4 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 September 2023.

5 ClinicalTrials.gov. A Study of Combination Amivantamab and Carboplatin-Pemetrexed 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 September 2023.

6 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 September 2023.

7 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 September 2023.

8 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 September 2023.

9 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 September 2023.

10 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 September 2023.

11 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 September 2023.

12 ClinicalTrials.gov. A Study of Combination Therapy With Amivantamab and Cetrelimab in Participants With Metastatic Non-small Cell Lung Cancer (PolyDamas). Available at: https://www.clinicaltrials.gov/study/NCT05908734?term=polydamas&rank=1. Accessed September 2023.

13 ClinicalTrials.gov. Premedication to Reduce Amivantamab Associated Infusion-Related Reactions (SKIPPirr). Available at: https://classic.clinicaltrials.gov/ct2/show/NCT05663866. Accessed September 2023.

14 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. https://doi.org/10.1200/JCO.23.00515. https://doi.org/10.1200/JCO.23.00515" target="_blank">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

15 The World Health Organization. Cancer. https://www.who.int/news-room/fact-sheets/detail/cancer. Accessed September 2023.

16 American Cancer Society. What is Lung Cancer? https://www.cancer.org/content/cancer/en/cancer/lung-cancer/about/what-is.html. Accessed September 2023.

17 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.

18 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.

19 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 epidermal growth factor receptor-mutant non-small cell lung cancer. J Clin Oncol. 37:97-104.

20 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.

21 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.

22 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.

23 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 September 2023.

24 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.

25 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.

26 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: The Janssen Pharmaceutical Companies of Johnson & Johnson