RYBREVANT®▼ (amivantamab) plus chemotherapy shows positive overall survival trend versus chemotherapy in patients with previously treated EGFR-mutated lung cancer

Post-progression outcomes showed significant and sustained improvement for amivantamab plus chemotherapy versus chemotherapy alone¹

BEERSE, BELGIUM , Sept. 14, 2024 (GLOBE NEWSWIRE) — Janssen-Cilag International NV, a Johnson & Johnson company, today announced updated results from the Phase 3 MARIPOSA-2 study which showed RYBREVANT^®▼ (amivantamab) combined with chemotherapy led to consistent benefit across post-progression outcomes in adult patients with previously treated non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations.¹  The data also reveal a favourable trend toward improved overall survival (OS) compared to chemotherapy alone.¹ Results were presented at the at the European Society of Medical Oncology (ESMO) 2024 Congress, taking place in Barcelona, Spain from 13-17 September.¹

“The positive overall survival trend seen in MARIPOSA-2 suggests that amivantamab combined with chemotherapy could potentially change the treatment landscape for a population that has historically faced limited options,” said Prof. Sanjay Popat, FRCP, Ph.D., Medical Oncologist at the Royal Marsden Hospital and the Institute of Cancer Research in the United Kingdom, and presenting author.* “Building on the strong progression-free survival data previously reported from this study and by helping more patients stay on treatment for longer, we are improving their chances for better outcomes.”

At the second interim analysis, with a median follow-up of 18.1 months, 50 percent of patients treated with amivantamab plus chemotherapy were still alive at the 18-month landmark, compared to 40 percent of those receiving chemotherapy alone (median OS, 17.7 vs 15.3 months, respectively; hazard ratio [HR], 0.73; [95 percent confidence interval [CI], 0.54–0.99]; nominal P=0.039**).¹ Amivantamab plus chemotherapy showed a significant improvement in treatment discontinuation rates, with nearly five times as many patients remaining on therapy at 18 months (22 percent) compared to chemotherapy (4 percent) (median time-to-treatment discontinuation [TTD], 10.4 vs 4.5 months, respectively) [95 percent CI, 0.33–0.53]; nominal P<0.0001**.¹ Additionally, patients treated with amivantamab plus chemotherapy experienced a 27 percent reduction in the risk of symptomatic progression (median time to symptomatic progression [TTSP], 16.0 vs 11.8 months; HR, 0.73; [95 percent CI, 0.55–0.96]; nominal P=0.026**).¹ The time to subsequent therapy was significantly prolonged with the amivantamab combination compared to chemotherapy (median time to subsequent therapy [TTST], 12.2 vs 6.6 months, respectively; HR, 0.51; [95 percent CI, 0.39–0.65]; nominal P<0.0001**), which also reduced the risk of second disease progression or death by 36 percent (median progression-free survival 2 [PFS2], 16.0 vs 11.6 months, respectively; HR, 0.64; [95 percent CI, 0.48–0.85]; nominal P=0.002**).¹

“Despite the challenge of diverse resistance mechanisms in EGFR-mutant non-small cell lung cancer, the MARIPOSA-2 data demonstrate that combining amivantamab with chemotherapy significantly prolongs progression-free survival after subsequent therapy and shows the potential for improved overall survival compared to chemotherapy alone,” said Henar Hevia, Ph.D., Senior Director, EMEA Therapeutic Area Lead, Oncology,  Johnson & Johnson Innovative Medicine. “These results reinforce our commitment to advancing precision medicine, delivering novel mechanisms of action, and ultimately more durable treatment options to improve outcomes for patients in need of new hope.’’

In the primary analysis of the MARIPOSA-2 study, presented at the European Society for Medical Oncology (ESMO) 2023 Congress, adverse events (AEs) of Grade 3 or higher, mainly due to haematologic toxicities, were reported by 72 percent of patients treated with amivantamab plus chemotherapy, and 48 percent with chemotherapy alone.² The most common Grade 3 or higher AEs included neutropenia, thrombocytopenia, anaemia, and leukopenia.² Grade 3 or 4 bleeding events were seen in one percent of patients treated with amivantamab plus chemotherapy, and in no patients with chemotherapy.² Serious treatment-emergent AEs (TEAEs) were observed in 32 percent of patients treated with amivantamab plus chemotherapy and 20 percent with chemotherapy.² The most common serious TEAEs were thrombocytopenia, neutropenia, and febrile neutropenia. ² Infusion-related reactions occured in 58 percent (all grades) of patients on aminvantamab plus chemotherapy.² Treatment-related AEs leading to death were infrequent in all arms (2 percent vs. 0.4 percent) in the amivantamab plus chemotherapy and chemotherapy alone arms respectively.² Permanent discontinuation of all study agents in amivantamab plus chemotherapy arm due to adverse reactions occurred in 11 (8 percent) patients.²

“We are pleased to see that amivantamab plus chemotherapy continues to show improved survival outcomes after a year and a half of follow-up, providing real benefits to patients with few other options,” said Joshua Bauml, M.D., Vice President, Lung Cancer Disease Area Stronghold Leader, Johnson & Johnson Innovative Medicine. “These results underscore the potential of this combination regimen to make a meaningful difference for patients, and we anticipate continued improvement as we move toward the final analysis.”

Amivantamab plus chemotherapy received approval from the European Commision in August 2024 for the treatment of adults with advanced NSCLC with EGFR ex19del or L858R mutations, after failure of prior therapy including an EGFR tyrosine kinase inhibitor (TKI), based upon the MARIPOSA-2 study.³

About MARIPOSA-2   
MARIPOSA-2 (NCT04988295), which enrolled 657 patients, is a randomised, open-label Phase 3 study evaluating the efficacy and safety of two combination regimens of amivantamab (with and without lazertinib) and chemotherapy.² Patients with locally-advanced or metastatic EGFR ex19del or exon 21 L858R substitution NSCLC who had disease progression on or after treatment with osimertinib were randomised to treatment with amivantamab plus chemotherapy, amivantamab plus chemotherapy with lazertinib, or chemotherapy alone.² The dual primary endpoint was used to compare the progression-free survival (PFS) (using RECIST v1.1 guidelines^†) as assessed by blinded independent central review (BICR) for each experimental arm to chemotherapy alone.² Secondary endpoints included objective response as assessed by BICR, overall survival (OS), duration of response (DOR), time to subsequent therapy, PFS2 and intracranial PFS.²

All study participants underwent serial brain imaging to allow for the robust assessment of intracranial endpoints and to assess the CNS activity of amivantamab and platinum doublet chemotherapy with and without lazertinib.² Because brain metastases can lead to significant burden and poor outcomes for patients, this aspect of the study design provides critical information in an area of high unmet need.⁴

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 TKI

In February 2024, a Type II extension of indication application was submitted to the European Medicines Agency (EMA) based on the MARIPOSA study, for amivantamab in combination with lazertinib for the first-line treatment of adult patients with advanced 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 Lazertinib
In 2018, Janssen Biotech, Inc., entered into a license and collaboration agreement with Yuhan Corporation for the development of 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.¹² An analysis of the efficacy and safety of lazertinib from the Phase 3 study LASER301 was published in The Journal of Clinical Oncology in 2023.¹² In December 2023, a marketing authorisation application (MAA) was submitted to the EMA seeking approval of lazertinib, in combination with amivantamab for the first-line treatment of adult patients with advanced NSCLC with common EGFR mutations including exon 19 deletions or L858R substitution mutations.¹³

About Non-Small Cell Lung Cancer
In Europe, it is estimated that 484,306 people were diagnosed with lung cancer in 2022.¹⁴ NSCLC accounts for 85 percent of all lung cancer cases.¹⁵ Lung cancer is Europe’s biggest cancer killer, with more deaths than breast cancer and prostate cancer combined.¹⁴

The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.¹⁵ Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.^15,16 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 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.²¹ The five-year survival rate for patients with advanced NSCLC and EGFR mutations treated with EGFR tyrosine kinase inhibitors (TKIs) is less than 20 percent.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 www.janssen.com/emea. Follow us at www.linkedin.com/company/jnj-innovative-medicine-emea Janssen Research & Development, LLC, Janssen-Cilag, S.A., Janssen Biotech, Inc. 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. 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 http://www.sec.gov/, http://www.jnj.com/ 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.    

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*Prof. Sanjay Popat has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work.

**P-value is from a log-rank test stratified by osimertinib line of therapy (first-line vs second-line), history of brain metastases (yes or no), and Asian race (yes vs no). OS was evaluated at a 2-sided alpha of 0.0142.

 ^†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 Popat, et al. Overall Survival Among Patients Receiving Amivantamab Plus Chemotherapy vs Chemotherapy in EGFR-mutated, Advanced Non-small Cell Lung Cancer After Disease Progression on Osimertinib (MARIPOSA-2). 2024 European Society for Medical Oncology. September 14, 2024.

² Passaro A, et al. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Annals of Oncology 2024;35(1):77-90.

³ Janssen.com/EMEA. European Commission approves RYBREVANT^®▼ (amivantamab) in combination with chemotherapy for the treatment of adult patients with advanced EGFR-mutated nonsmall cell lung cancer after failure of prior therapy. Available at: https://www.janssen.com/emea/sites/www_janssen_com_emea/files/jj_emea_mariposa-2_ec_press_release_2024.pdf. Accessed September 2024.

⁴ Fuchs J, et al. Resection of isolated brain metastases in non-small cell lung cancer (NSCLC) patients – evaluation of outcome and prognostic factors: A retrospective multicenter study. PLoS ONE 16(6):e0253601. https://doi.org/10.1371/journal.pone.0253601.

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. August 2024. Available at https://www.ema.europa.eu/en/documents/product-information/rybrevant-epar-product-information_en.pdf. 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. https://www.janssen.com/emea/sites/www_janssen_com_emea/files/amivantamab_mariposa_ema_filing_release_2024_2.pdf  Accessed: September.

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: https://www.janssen.com/sites/www_janssen_com_emea/files/jj_asco_paloma-3_-_ema_filing_press_release.pdf. Accessed: September 2024.

¹² Cho, BC, et al. Lazertinib versus gefitinib as first-line treatment in patients with EGFR-mutated advanced nonsmall-cell lung cancer: Results From LASER301. J Clin Oncol. 2023;41(26):4208-4217.

¹³ Janssen.com/EMEA. Janssen Submits Marketing Authorisation Application to the European Medicines
Agency Seeking Approval of Lazertinib, in combination with RYBREVANT^®▼
(amivantamab), for the First-Line Treatment of Patients with EGFR-Mutated NonSmall Cell Lung Cancer. Available at: https://www.janssen.com/emea/sites/www_janssen_com_emea/files/lazertinib_ema_filing_press_release_december_2023.pdf. Accessed: September 2024.

¹⁴ Global Cancer Observatory. Cancer Today. Available at: https://gco.iarc.who.int/media/globocan/factsheets/populations/908-europe-fact-sheet.pdf.  Accessed: September 2024.

¹⁵ Zappa C, et al. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res 2016;5(3):288–300.

¹⁶ Wee P & Wang Z. Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways. Cancers 2017;9(12):52.

¹⁷ 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.

¹⁸ 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.

¹⁹ 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.

²⁰ 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.

²¹ American Lung Association. EGFR and Lung Cancer. Available at: https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/egfr. Accessed: September 2024.

²² Lin JJ, et al. Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs. J Thorac Oncol 2016;11(4):556-65.

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