RYBREVANT® plus chemotherapy approved in Canada as first and only targeted treatment to reduce risk of disease progression or death by more than half in second-line EGFR-mutated advanced lung cancer

Phase 3 MARIPOSA-2 study showed RYBREVANT^® in combination with carboplatin and pemetrexed significantly improved progression-free survival compared to carboplatin and pemetrexed alone.¹

TORONTO, Jan. 16, 2025 /CNW/ - Johnson & Johnson (NYSE: JNJ) announced today that Health Canada has issued a Notice of Compliance (NOC) for RYBREVANT^® (amivantamab for injection) in combination with carboplatin and pemetrexed (platinum-based chemotherapy) for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) Exon 19 deletions or Exon 21 L858R substitution mutations, whose disease has progressed on or after treatment with osimertinib.¹

"Patients with EGFR-mutated advanced NSCLC treated with osimertinib inevitably develop resistance mechanisms and face poor outcomes on platinum-based chemotherapy alone," says Dr. Barbara Melosky*, Professor of Medicine, University of British Columbia. "RYBREVANT^® (amivantamab) plus platinum-based chemotherapy has the potential to address treatment resistance, support prolonged progression-free survival (PFS), and improve overall response."

Lung cancer remains the most commonly diagnosed cancer in Canada and the leading cause of cancer death.² NSCLC accounts for 88 per cent of all lung cancers in Canada.³ Globally, approximately one-third of patients with NSCLC harbour an EGFR mutation with 85-90 per cent comprised of exon 19 deletions and exon 21 L858R substitution mutations.^4,5 The five-year survival rate for people with advanced EGFR-mutated NSCLC is less than 20 per cent.⁶ Acquired resistance mechanisms after tyrosine kinase inhibitor (TKI) monotherapy can make subsequent treatment more difficult, and there is limited evidence supporting the efficacy of TKI recycling post-TKI progression.^7,8 The addition of immunotherapy to chemotherapy for EGFR-mutated NSCLC has also failed to demonstrate clinically meaningful improvements in PFS in this population.^9,10

"Our understanding of genetic alterations such as EGFR mutations has allowed new and exciting anti-cancer therapies to improve survival in patients diagnosed with these diseases. However, there are still significant treatment gaps we need to bridge in all lines of treatment," says Dr. Scott Owen**, Medical Oncologist, McGill University Health Center. "This approval in the second-line setting has the potential to redefine the standard of care, offering improved patient outcomes both in terms of clinical efficacy and quality of life."

"A lung cancer diagnosis can be devastating. This approval of RYBREVANT^® is welcome news for patients, offering hope against this difficult-to-treat disease and a chance to spend more quality time with their loved ones," says Shem Singh***, Executive Director, Lung Cancer Canada. "Having this new therapeutic option underscores the importance of ongoing research and innovation and is another step forward for people living with EGFR-mutated advanced lung cancers where significant unmet needs remain."

This Health Canada NOC is based on results from the Phase 3, randomized, open-label, multicentre MARIPOSA-2 study.¹ The study compared treatment with RYBREVANT^® in combination with carboplatin and pemetrexed to treatment with platinum-based chemotherapy alone in patients with locally advanced or metastatic NSCLC with EGFR Exon 19 deletions or Exon 21 L858R substitution mutations who had previously received osimertinib as first- or second-line therapy.¹ A total of 394 patients were randomized to receive RYBREVANT^® in combination with platinum-based chemotherapy (N=131) or only platinum-based chemotherapy (N=263).¹ The results demonstrated a clinically meaningful improvement in PFS, with a median of 6.3 months for patients who received RYBREVANT^® plus platinum-based chemotherapy compared to 4.2 months for patients who received platinum-based chemotherapy (HR, 0.48, 95% CI, 0.36-0.64, P<0.0001), corresponding to a 52 per cent reduction in the risk of disease progression or death compared to platinum-based chemotherapy.¹ Additionally, the overall response rate (ORR) analysis showed significantly improved anti-tumor activity with an ORR of 63.8% in the RYBREVANT^® plus platinum-based chemotherapy arm compared to 36.2% in the platinum-based chemotherapy arm.^1,11

The median duration of treatment was 6.3 months for patients who received RYBREVANT^® in combination with platinum-based chemotherapy (N=130) and 3.7 months for those who received platinum-based chemotherapy alone (N=243).¹ The most common adverse reactions (≥ 20 per cent) were infusion related reactions, neutropenia, nausea, rash, thrombocytopenia, anemia, constipation, paronychia, edema peripheral, stomatitis, decreased appetite, leukopenia, fatigue, asthenia, vomiting, hypoalbuminemia, COVID-19, alanine aminotransferase increased, and dermatitis acneiform.¹ Serious adverse reactions in > 2 per cent of patients included thrombocytopenia, dyspnea, sepsis, and pulmonary embolism.¹

Fifteen per cent of patients permanently discontinued RYBREVANT^® due to adverse reactions.¹ The most frequent adverse reactions leading to treatment discontinuation in ≥ 1 per cent of patients were infusion-related reactions.¹ The most common Grade 3 to 4 laboratory abnormalities (≥ 2 per cent) were decreased albumin, increased alanine aminotransferase, increased gamma‑glutamyl transferase, decreased sodium, decreased potassium, and decreases in white blood cells, hemoglobin, neutrophils, platelets, and lymphocytes.¹

"At Johnson & Johnson, we are dedicated to advancing scientific innovations targeting novel disease pathways and enabling patients diagnosed with lung cancer to receive treatment that is optimized for their specific disease," says Berkeley Vincent, President, Johnson & Johnson Innovative Medicine, Canada. "The encouraging results from the MARIPOSA-2 study demonstrate a significant benefit in progression-free survival in the post-osimertinib setting, reinforcing the potential of RYBREVANT^® plus platinum-based chemotherapy in this patient population. Today's approval marks another important milestone in our pursuit to get in front of cancer."

About RYBREVANT^®

RYBREVANT^® 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.¹ It binds extracellularly, or to the outside of the cell, slowing or inhibiting tumour growth and leading to tumour cell death.¹ RYBREVANT^®, indicated as a monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with activating EGFR Exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy, has been issued a marketing authorization with conditions.¹ RYBREVANT^®, indicated in combination with platinum-based chemotherapy (carboplatin and pemetrexed) for the first-line treatment of adult patients with locally advanced (not amenable to curative therapy) or metastatic NSCLC with activating EGFR Exon 20 insertion mutations, has been issued a market authorization without conditions.¹ RYBREVANT^®, in combination with platinum-based chemotherapy (carboplatin and pemetrexed) for the treatment of patients with locally advanced or metastatic NSCLC with EGFR Exon 19 deletions or Exon 21 L858R substitution mutations, whose disease has progressed on or after treatment with osimertinib, has been issued a market authorization without conditions.¹ A validated test is required to identify EGFR Exon 20 insertion, EGFR Exon 19 deletion or Exon 21 L858R substitution mutation-positive status prior to treatment.¹

About the MARIPOSA-2 Study

MARIPOSA-2 (NCT04988295, NSC3002) is a randomized, open-label, multicentre Phase 3 study evaluating the efficacy and safety of two combination regimens of RYBREVANT^® (with and without lazertinib) and platinum-based chemotherapy. Patients with locally advanced or metastatic EGFR Exon 19 deletions or Exon 21 L858R substitution NSCLC who had disease progression on or after treatment with osimertinib were randomized to treatment with RYBREVANT^® plus platinum-based chemotherapy, RYBREVANT^® plus platinum-based chemotherapy with lazertinib, or platinum-based chemotherapy alone. The dual primary endpoint was used to compare the PFS (using RECIST v1.1 guidelines^§) as assessed by blinded independent central review (BICR) for each experimental arm to platinum-based chemotherapy alone. Secondary endpoints included objective response as assessed by BICR, Overall Survival (OS), duration of response (DOR), time to subsequent therapy (TTST), and PFS after first subsequent therapy (PFS2) and intracranial PFS.¹²

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 and https://innovativemedicine.jnj.com/canada. Follow us on LinkedIn at Johnson & Johnson Innovative Medicine, Canada and X at @JNJInnovMedCAN. Janssen Inc. is a Johnson & Johnson company.

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 RYBREVANT^® (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 materialize, actual results could vary materially from the expectations and projections of Janssen Inc. and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended 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 www.sec.gov, www.jnj.com or on request from Johnson & Johnson. Neither of Janssen Inc. nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

* Dr. Barbara Melosky was not compensated for this media work. She has been compensated previously by Janssen Inc., a Johnson & Johnson company, for other professional engagements.

** Dr. Scott Owen was not compensated for this media work. He has been compensated previously by Janssen Inc., a Johnson & Johnson company, for other professional engagements.

*** Shem Singh was not compensated for this media work. He has not been compensated previously by Janssen Inc., a Johnson & Johnson company, for other professional engagements.

© Johnson & Johnson and its affiliates 2025

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¹ RYBREVANT^® Product Monograph, Toronto, ON: Janssen Inc. January 13, 2025.

² Canadian Cancer Society. Lung and bronchus cancer statistics. https://cancer.ca/en/cancer-information/cancer-types/lung/statistics

³ Canadian Cancer Society. Canadian Cancer Statistics – a 2020 special report on lung cancer. p.14. https://cdn.cancer.ca/-/media/files/cancer-information/resources/publications/2020-canadian-cancer-statistics-special-report/2020-canadian-cancer-statistics-special-report-en.pdf

⁴ Soo, Ross A et al. "Prevalence of EGFR Mutations in Patients With Resected Stages I to III NSCLC: Results From the EARLY-EGFR Study." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer vol. 19,10 (2024): 1449-1459. doi:10.1016/j.jtho.2024.06.008

⁵ Harrison, Peter T et al. "Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer." Seminars in cancer biology vol. 61 (2020): 167-179. doi:10.1016/j.semcancer.2019.09.015

⁶ Lin, Jessica J et al. "Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer vol. 11,4 (2016): 556-65. doi:10.1016/j.jtho.2015.12.103

⁷ Koulouris, Andreas et al. "Resistance to TKIs in EGFR-Mutated Non-Small Cell Lung Cancer: From Mechanisms to New Therapeutic Strategies." Cancers vol. 14,14 3337. 8 Jul. 2022, doi:10.3390/cancers14143337

⁸ Aredo, Jacqueline V et al. "Afatinib After Progression on Osimertinib in EGFR-Mutated Non-Small Cell Lung Cancer." Cancer treatment and research communications vol. 30 (2022): 100497. doi:10.1016/j.ctarc.2021.100497

⁹ Mok, Tony et al. "Nivolumab Plus Chemotherapy in Epidermal Growth Factor Receptor-Mutated Metastatic Non-Small-Cell Lung Cancer After Disease Progression on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Final Results of CheckMate 722." Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 42,11 (2024): 1252-1264. doi:10.1200/JCO.23.01017

¹⁰ Yang JCH, et al. Pemetrexed and platinum with or without pembrolizumab for tyrosine kinase inhibitor (TKI)-resistant, EGFR-mutant, metastatic nonsquamous NSCLC: Phase 3 KEYNOTE-789 study. Abstract. J Clin Oncol. 2023.41(17): doi:10.1200/JCO.2023.41.17_suppl.LBA9000 

¹¹ CR and PR do not have to be confirmed. Percent of Responder is based on the number of subjects with measurable disease at baseline

¹² 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://clinicaltrials.gov/ct2/show/NCT04988295 

SOURCE Janssen Inc.

Media contact: Michael McDougall, [email protected], 416-568-9481; Investor contact: Lauren Johnson, [email protected]