Health Canada authorizes LAZCLUZE® (lazertinib) in combination with RYBREVANT® (amivantamab) as a first-line chemotherapy-free treatment for patients with EGFR-mutated advanced lung cancer

Phase 3 MARIPOSA study showed LAZCLUZE^® plus RYBREVANT^® significantly improved progression-free survival, reducing the risk of disease progression or death by 30 per cent versus osimertinib alone.¹

TORONTO, March 10, 2025 /CNW/ - Johnson & Johnson (NYSE: JNJ) announced today that Health Canada has issued a Notice of Compliance (NOC) for LAZCLUZE^® (lazertinib) in combination with RYBREVANT^® (amivantamab) 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.¹ Janssen Inc., a Johnson & Johnson company, is the market authorization holder for LAZCLUZE ^® and RYBREVANT^® in Canada.

With this authorization, LAZCLUZE^® plus RYBREVANT^® becomes the first and only chemotherapy-free combination regimen showing clinically meaningful and statistically significant improvement in progression-free survival versus osimertinib for these patients.¹ RYBREVANT^® is a fully human bispecific antibody targeting EGFR and MET with immune cell-directing activity, and LAZCLUZE^® is a highly potent, brain penetrant,² third-generation EGFR tyrosine kinase inhibitor (TKI).^3,1

"While we have seen much progress in the treatment of lung cancer, many patients with EGFR-mutated NSCLC don't reach second-line therapy when initial treatment stops working. This underscores the critical need for better options in the first-line setting," says Dr. Natasha Leighl*, Lung Site Lead, Medical Oncology at the Princess Margaret Cancer Centre, and Professor of Medicine at the University of Toronto. "The approval of this new targeted combination represents a significant advance in treatment, providing patients with a new option that extends progression-free survival and survival in the first line compared to previously available treatments." 

Lung cancer remains the most commonly diagnosed cancer in Canada and the leading cause of cancer death.⁴ NSCLC accounts for 88 per cent of all lung cancers in Canada.⁵ Globally, approximately one third of patients with NSCLC harbour an EGFR mutation, 27-38 per cent of whom never receive second-line therapy due to disease progression and limited treatment options.^6,7,8 The five-year survival rate for people with advanced EGFR-mutated NSCLC is less than 20 per cent and complex acquired resistance mechanisms after TKI monotherapy make subsequent treatment more difficult. ^9,10

"Each breakthrough in the treatment of lung cancer provides new hope for patients," says Shem Singh***, Executive Director of Lung Cancer Canada. "Findings from the MARIPOSA study show new progress in the treatment of NSCLC with EGFR mutations, including a meaningful increase in progression-free survival. The approval of the combination of LAZCLUZE and RYBREVANT allows for this valuable novel first-line approach to be used in the treatment of these cancers, which is good news for people diagnosed with this disease and their families." 

The Health Canada NOC is based on results from the Phase 3 MARIPOSA study, which showed LAZCLUZE^® plus RYBREVANT^® reduced the risk of disease progression or death by 30 per cent compared with osimertinib (median progression-free survival (PFS) was 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. The median duration of response (DOR) was nine months longer with LAZCLUZE^® plus RYBREVANT^® versus osimertinib (25.8 months versus 16.7 months), a secondary endpoint of the study.¹

Among the 421 patients who received LAZCLUZE^® in combination with RYBREVANT^®, 83.6 per cent were exposed to LAZCLUZE^® for 6 months or longer and 73.2 per cent were exposed to LAZCLUZE^® for greater than 1 year.¹ Serious adverse reactions in >2% of patients who received LAZCLUZE in combination with amivantamab included pulmonary embolism (6.2%), pneumonia (4.0%), deep vein thrombosis (2.9%), ILD/pneumonitis (2.9%), COVID-19 (2.4%) infusion related reaction (2.1%; amivantamab-specific), rash (2.1%) and pleural effusion (2.1%).¹

"This approval strengthens our commitment to redefining care in areas of high unmet need by advancing innovative regimens that have the potential to extend survival in this deadly disease," says Berkeley Vincent, President, Johnson & Johnson Innovative Medicine, Canada. "Today's Health Canada authorization for LAZCLUZE in combination with RYBREVANT further reinforces the critical role of precision medicine in driving enhanced outcomes for patients living with lung cancer. By offering this targeted first-line treatment, we are continuing our efforts to alter the trajectory of this disease."

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 2023.¹¹ 

About RYBREVANT^®
RYBREVANT® (amivantamab-vmjw), a fully human bispecific antibody targeting EGFR and MET with immune cell-directing activity, It binds extracellularly, or to the outside of the cell, slowing or inhibiting tumour growth and leading to tumour cell death.³

RYBREVANT^® has been issued a marketing authorization with conditions 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.³ It has also been granted market authorization, 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 and 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.3 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.³

About the MARIPOSA Study
MARIPOSA is a randomized, active-controlled, multicenter phase 3 study assessing the efficacy and safety of LAZCLUZE^® in combination with RYBREVANT^® as compared to osimertinib monotherapy as first-line treatment in patients with EGFR-mutated locally advanced or metastatic NSCLC not amenable to curative therapy.  A third, LAZCLUZE^® monotherapy arm was included to demonstrate contribution of components, but was not powered for a direct comparison.  Patient samples were required to have one of the two common EGFR mutations (exon 19 deletion or exon 21 L858R substitution mutation), as identified by local testing. A total of 1074 patients were randomized (2:2:1) to receive LAZCLUZE^® in combination with RYBREVANT^®, osimertinib monotherapy, or LAZCLUZE^® monotherapy (an unapproved regimen for NSCLC) until disease progression or unacceptable toxicity. LAZCLUZE^® was administered at 240 mg orally once daily. RYBREVANT^® was administered intravenously at 1050 mg (for patients < 80 kg) or 1400 mg (for patients ≥ 80 kg) once weekly for 4 weeks, then every 2 weeks thereafter starting at week 5. Osimertinib was administered at a dose of 80 mg orally once daily.¹

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 LAZCLUZE^® (lazertinib) and RYBREVANT^®. 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 most recent Annual Report on Form 10-K, 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. None 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. Natasha Leighl was not compensated for this media work. Dr. Leighl has been compensated previously by J&J for other professional engagements.

*** Shem Singh has not received compensation from J&J. The company has provided funding to Lung Cancer Canada for other initiatives.

© Johnson & Johnson and its affiliates 2025

______________________________________
1	LAZCLUZE^® Product Monograph, Toronto, ON: Janssen Inc. March 6, 2025.
2	Yun J, Hong MH, Kim SY, et al. YH25448, an irreversible EGFR-TKI with potent intracranial activity in EGFR mutant non–small cell lung cancer. Clin Cancer Res. 2019;25:2575–2587.
3	RYBREVANT^® Product Monograph, Toronto, ON: Janssen Inc. January 13, 2025.
4	Canadian Cancer Society. Lung and bronchus cancer statistics. https://cancer.ca/en/cancer-information/cancer-types/lung/statistics
5	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
6	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.
7	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.
8	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
9	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
10	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
11	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. Journal of clinical oncology vol. 41, no. 26. (2023): 4208-4222. doi/10.1200/JCO.23.00515

SOURCE Janssen Inc.

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