MHRA grants marketing authorisation for LAZCLUZE®▼ (lazertinib) in combination with RYBREVANT®▼ (amivantamab) for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations

Non-small cell lung cancer is the most common type of lung cancer, accounting for 80-85 percent of all cases¹

EGFR mutations are found in around 15 percent of cases of NSCLC in Western patients, and most of those mutations are exon 19 deletions or exon 21 L858R substitution mutations^2,3

High Wycombe, UK (19 March 2025) – Johnson & Johnson has announced that the Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorisation for LAZCLUZE®▼ (lazertinib) in combination with RYBREVANT®▼ (amivantamab) for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations.^4,5

Non-small cell lung cancer is the most common type of lung cancer, accounting for 80-85 percent of all cases.¹ EGFR mutations are found in around 15 percent of cases of NSCLC in Western patients, and most (85-90 percent) of those mutations are exon 19 deletions or exon 21 L858R substitution mutations.^2,3

“We are delighted that the MHRA has granted marketing authorisation for this treatment combination, adding a first-line option for people with a common type of lung cancer in the UK,” said Dr. John Fleming, Country Medical Director, Johnson & Johnson Innovative Medicine UK. “This approval marks an extremely important step in J&J’s commitment to supporting the lung cancer community and delivering innovative precision therapies to people with cancer. As we look to progress with HTA submissions for lazertinib with amivantamab in the coming months, we hope to continue our mission of getting in front of cancer and ensure eligible patients can access this treatment via the NHS as quickly as possible.”

Lazertinib is a once-daily EGFR tyrosine kinase inhibitor (TKI), which works by blocking EGFR mutations.^3,4,5 Amivantamab is a bispecific EGFR and mesenchymal epithelial transition (MET) antibody that has immune cell-directing activity.³ The five-year survival rate for patients with advanced NSCLC and EGFR mutations treated with TKIs is less than 20 percent, and 25 percent of patients receiving the current first-line standard of care, osimertinib, do not survive long enough to reach second-line treatment – demonstrating the need for additional treatment options in the first-line setting.^6,7

#ENDS#

About the MARIPOSA study
Today’s MHRA authorisation is based on MARIPOSA, a randomised, open-label, active-controlled, multicentre phase 3 study assessing the efficacy and safety of lazertinib in combination with amivantamab compared to osimertinib monotherapy in the first-line treatment of patients with EGFR-mutated locally advanced or metastatic NSCLC with exon 19 deletion or exon 21 L858R substitution mutations.^4,5 The primary endpoint of this study was progression-free survival (PFS), with secondary endpoints being overall survival (OS), objective response (OR), duration of response (DOR) and safety.³

The study met its primary endpoint of PFS, and at median follow-up of 22 months, amivantamab plus lazertinib reduced the relative risk of disease progression or death by 30 percent compared to osimertinib (median PFS: 23.7 months versus 16.6 months; hazard ratio [HR]=0.70; 95 percent confidence interval [CI], 0.58–0.85; P<0.001) as assessed by blinded independent central review (BICR).³ The absolute risk of disease progression or death was reduced by 14%.⁸

In the dataset of amivantamab in combination with lazertinib (N=421), the most frequent adverse reactions in all grades were rash (89%), nail toxicity (71%), infusion-related reactions (IRR) (63%), hypoalbuminaemia (48%), oedema (47%), stomatitis (43%), venous thromboembolism (VTE) (36%), alanine aminotransferase increased (36%), fatigue (32%), aspartate aminotransferase increased (29%), diarrhoea (29%), constipation (29%), dry skin (26%), pruritic (24%), decreased appetite (24%), hypocalcaemia (21%), nausea (21%) and other eye disorders (21%).⁵ The most frequent serious adverse reactions included VTE (11%), interstitial lung disease (ILD) (2.9%), rash (2.4%), and IRR (2.1%).⁵ Twenty-two percent of patients discontinued amivantamab due to adverse reactions.5 The most frequent adverse reactions leading to treatment discontinuation were rash (5.5%), IRR (4.5%), nail toxicity (3.6%), ILD (2.9%) and VTE (2.9%).⁵ The most frequent adverse reactions leading to lazertinib treatment discontinuation were ILD (2.9%), VTE (1.7%), and rash (1.2%).⁴ Please refer to the individual amivantamab and lazertinib Summary of Product Characteristics for safety information on the individual products.

The MARIPOSA study required all patients to have serial brain imaging with magnetic resonance imaging (MRI), which is important for a disease where almost 30 percent of patients develop brain metastases.^4,5,9 The primary endpoint of PFS in MARIPOSA included these central nervous system (CNS) events detected by serial brain MRIs.^4,5 The median PFS when censoring CNS-only first progressions was 27.5 months for the combination of amivantamab and lazertinib, compared to 18.4 months for osimertinib (HR=0.68; 95 percent CI, 0.55–0.83; P<0.0001).^4,5

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.¹⁰ An analysis of the efficacy and safety of lazertinib from the Phase 3 study LASER301 was published in The Journal of Clinical Oncology in 2023.¹⁰

Adverse events should be reported. ▼ This medicinal product is subject to additional monitoring, and it is therefore important to report any suspected adverse events related to this medicinal product. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk/ or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Janssen-Cilag Limited, a Johnson & Johnson company on 01494 567447 or at [email protected].

About amivantamab
Amivantamab is a fully-human EGFR-MET bispecific antibody that acts by targeting tumours with activating and resistant EGFR mutations and MET mutations and amplifications, and by harnessing the immune system.^11,12,13,14 Amivantamab is licensed for treating adults in Great Britain and Northern Ireland:

• in combination with lazertinib for the first-line treatment of adult patients with advanced NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations;
• in combination with carboplatin and pemetrexed for the treatment of adult patients with advanced NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations after failure of prior therapy including an EGFR TKI;
• 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.⁵

Adverse events should be reported. ▼ This medicinal product is subject to additional monitoring, and it is therefore important to report any suspected adverse events related to this medicinal product. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk/ or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Janssen-Cilag Limited, a Johnson & Johnson company on 01494 567447 or at [email protected].

About non-small cell lung cancer
Lung cancer is the third most common cancer in the UK, and it is estimated that there are around 49,200 new lung cancer cases in the UK every year (2017-2019).¹⁵ Non-small cell lung cancer (NSCLC) is the most common type, accounting for 80-85 percent of all lung cancers.¹

The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.¹⁶ Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.^16,17 EGFR mutations are present in around 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients.^2,18,19,20 EGFR exon 19 deletion or EGFR L858R mutations are the most common EGFR mutations.² The five-year survival rate for patients with advanced NSCLC and EGFR mutations treated with EGFR TKIs is less than 20 percent.⁶

About Johnson & Johnson
Janssen, the Pharmaceutical Companies of Johnson & Johnson, has become Johnson & Johnson Innovative Medicine. The Company is updating its brand and uniting both its pharmaceutical and MedTech segments under the Johnson & Johnson brand name.

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://innovativemedicine.jnj.com/uk/.

Follow us at https://www.linkedin.com/company/jnjinnovativemedicineuk/ and www.x.com/JNJInnovMedUK.

© Janssen-Cilag Limited, a Johnson & Johnson Company. All rights reserved.

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 and lazertinib. 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 Limited 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, 2024, 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 Research & Development, LLC, Janssen Biotech, Inc. Janssen-Cilag Limited nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.