NICE issues Final Draft Guidance recommending RYBREVANT^®▼ (amivantamab) with LAZCLUZE™▼ (lazertinib) as a first-line treatment for adult patients with untreated advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations

The combination therapy offers a new chemotherapy-free first-line option for eligible patients with EGFR exon 19 deletions or exon 21 L858R substitution mutations¹

High Wycombe, UK (18 December 2025) – Johnson & Johnson has announced that the National Institute for Health and Care Excellence (NICE) has recommended RYBREVANT^®▼ (amivantamab) with LAZCLUZE™▼ (lazertinib), for use within its marketing authorisation, as an option for untreated advanced non-small cell lung cancer (NSCLC) in adults whose tumours have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, in its Final Draft Guidance.¹ This recommendation means that newly-diagnosed eligible patients may now be treated with amivantamab and lazertinib on the NHS in England and Wales.¹

Between 2019 and 2023, on average around 35,000 people were diagnosed with lung cancer in England.² NSCLC is the most common type of lung cancer, accounting for 80-85 percent of all cases.³ EGFR mutations are present in around 15 percent of cases of NSCLC in European patients, and most (85-90 percent) are exon 19 deletions or exon 21 L858R substitution mutations.^4,5 EGFR-positive NSCLC is more common in women than in men, those who do not smoke and people from Asian ethnic groups.¹

“EGFR+ UK welcomes NICE’s approval of amivantamab plus lazertinib for first-line treatment of eligible patients with common EGFR mutated NSCLC,” said Prof. Virginia Harrison, Research Trustee, EGFR+ UK.* “This is a meaningful advance for patients and their families facing this diagnosis. Importantly, it also provides something the EGFR community urgently needs: more choice in first-line treatment. Access to multiple effective options empowers patients and clinicians to tailor care to individuals’ needs and preferences, while maximising patient outcomes. This decision represents an important step in treatment options for people with EGFR-mutated lung cancer.”

“NICE’s recommendation represents a meaningful moment for the management of EGFR-mutated advanced NSCLC,” said Professor Sanjay Popat**, FRCP, Ph.D., Medical Oncologist at the Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, UK. “Access to additional first-line options on the NHS gives clinicians the flexibility to individualise treatment plans, which is essential in addressing the complex needs of this patient population. This milestone highlights the importance of continued progress in expanding treatment choice and supporting evidence-based care within the treatment pathway.”

The NICE recommendation is based on data from the Phase 3 MARIPOSA study, which met its primary endpoint of progression free survival (PFS), with patients receiving amivantamab with lazertinib living for a median of 23.7 months (95% confidence interval [CI], 19.1 to 27.7) without their disease worsening versus 16.6 months (95% CI, 14.8 to 18.5) in patients receiving osimertinib (hazard ratio for disease progression or death, 0.70; 95 percent CI, 0.58-0.85; p<0.001^†).⁶ Additionally, patients receiving amivantamab with lazertinib experienced significantly improved overall survival (OS) [secondary endpoint] versus those on osimertinib (hazard ratio for death, 0.75; 95 percent CI, 0.61-0.92; p<0.005).⁶ Median OS has not yet been reached (95 percent CI, 42.9-not reached [NR]) in patients treated with the combination versus 36.7 months (95 percent CI, 33.4-41.0) for patients treated with osimertinib.⁶

In the dataset of amivantamab (either intravenous or subcutaneous formulations) in combination with lazertinib (N=752), the most frequent adverse reactions of any grade (≥ 20 percent patients) were rash (87 percent), nail toxicity (67 percent), hypoalbuminaemia (48 percent), hepatotoxicity (43 percent), stomatitis (43 percent), oedema (42 percent), fatigue (35 percent), paraesthesia (29 percent), constipation (26 percent), diarrhoea (26 percent), dry skin (25 percent), decreased appetite (24 percent), nausea (24 percent), and pruritus (23 percent).⁷

“Today’s Final Draft Guidance from NICE represents an important step forward for people newly diagnosed with common EGFR mutated NSCLC in England and Wales,” said Amanda Cunnington, UK Senior Director of Patient Access, Johnson & Johnson Innovative Medicine. “The availability of a chemotherapy-free combination treatment will no doubt be welcome news to eligible patients and their loved ones. We are committed to working with partners across the healthcare system to ensure timely, equitable access to innovative therapies, and to support clinicians in delivering personalised care, enabling eligible patients to access advances seen in clinical data.”

#ENDS#

About the MARIPOSA study
MARIPOSA is a randomised-controlled, open-label, multicentre Phase 3 study assessing the efficacy and safety of amivantamab in combination with lazertinib 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.^5,6 The primary endpoint was PFS, and secondary endpoints included OS, objective response (OR), duration of response (DOR) and safety.⁵

The amivantamab plus lazertinib combination also met other secondary endpoints versus osimertinib including time to second disease progression or death (PFS2) and intra-cranial DOR.⁶ Notably, amivantamab and lazertinib prolonged time to symptomatic progression – the time from treatment randomisation to the onset of new or worsening lung cancer symptoms requiring intervention – by more than 14 months compared to osimertinib (43.6 months versus 29.3 months; hazard ratio, 0.69; 95 percent CI, 0.57-0.83; p<0.001^†).⁶

In the dataset of amivantamab (either intravenous or subcutaneous formulations) in combination with lazertinib (N=752), the most frequent adverse reactions of any grade (≥ 20 percent patients) were rash (87 percent), nail toxicity (67 percent), hypoalbuminaemia (48 percent), hepatotoxicity (43 percent), stomatitis (43 percent), oedema (42 percent), fatigue (35 percent), paraesthesia (29 percent), constipation (26 percent), diarrhoea (26 percent), dry skin (25 percent), decreased appetite (24 percent), nausea (24 percent), and pruritus (23 percent).⁷

Clinically relevant differences between the intravenous and subcutaneous formulations, when given in combination with lazertinib, were observed for administration-related reactions (63 percent for intravenous versus 14 percent for subcutaneous) and VTE (37 percent for intravenous versus 11 percent for subcutaneous).⁷

Serious adverse reactions were reported in 14 percent of patients who received amivantamab subcutaneous formulation in combination with lazertinib, including interstitial lung disease (ILD) (4.2 percent), VTE (2.7 percent), hepatotoxicity (2.1 percent), and fatigue (1.5 percent).⁷ Seven percent of patients discontinued amivantamab subcutaneous formulation due to adverse reactions.⁷ In patients treated with amivantamab subcutaneous formulation in combination with lazertinib, the most frequent adverse reactions of any grade (≥ 1 percent patients) leading to discontinuation of amivantamab subcutaneous formulation were ILD (3.6 percent) and rash (1.5 percent).⁷

The most frequent serious adverse reactions reported with the intravenous formulation included VTE (11 percent), ILD (2.9 percent), rash (2.4 percent), and infusion-related reactions (IRR) (2.1 percent).⁸ 22 percent of patients discontinued amivantamab-lazertinib due to adverse reactions.⁸ The most frequent adverse reactions leading to treatment discontinuation were rash (5.5 percent), IRR (4.5 percent), nail toxicity (3.6 percent), ILD (2.9 percent) and VTE (2.9 percent).⁸ Most adverse events were grade 1 and 2.⁸

About amivantamab
Amivantamab is a fully human bispecific antibody which targets both EGFR and MET.⁹ This makes amivantamab the first bispecific antibody targeting tumours with activating and resistant EGFR mutations, and MET mutations and amplifications, addressing two major mechanisms of resistance in NSCLC.^10,11,12

In the UK, amivantamab subcutaneous injection is indicated:

• 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;
• as monotherapy for treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations, after failure of platinum-based therapy.⁷

In the UK, amivantamab intravenous infusion is indicated:

• 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 tyrosine kinase inhibitor (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.⁸

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.¹³ An analysis of the efficacy and safety of lazertinib from the Phase 3 study LASER301 was published in The Journal of Clinical Oncology in 2023.¹³

In the UK, lazertinib in combination with amivantamab is indicated for the first-line treatment of adult patients with advanced NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations.¹⁴

About NSCLC
Lung cancer is the third most commonly diagnosed cancer in the UK, and a leading cause of cancer deaths.¹⁵ NSCLC is the most common type, accounting for 80-85 percent of all lung cancer types.³ 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 is a protein that plays a critical role in regulating the growth and division of healthy cells.¹⁶ In some patients with NSCLC, mutations in the gene responsible for EGFR lead to its overexpression.¹⁸ This abnormal activity can cause uncontrolled cell growth, ultimately driving the development and progression of cancer.¹⁶ EGFR mutations are present in around 15 percent of European patients with NSCLC with adenocarcinoma histology and occur in 40-50 percent of Asian patients.^{4,15,16,17,18} EGFR exon 19 deletion or EGFR L858R mutations are the most common EGFR mutations.¹³

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.

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Cautions Concerning Forward-Looking Statements
This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 related to 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 materialize, actual results could vary materially from the expectations and projections of Johnson & Johnson. Risks and uncertainties include, but are not limited to: competition, including technological advances, new products and patents attained by competitors; uncertainty of commercial success for new products; the ability of the company to successfully execute strategic plans; impact of business combinations and divestitures; challenges to patents; changes in behavior and spending patterns or financial distress of purchasers of health care products and services; and 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, www.investor.jnj.com or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments.

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*EGFR+ UK has not been paid for any media work.

**Professor Sanjay Popat has served as a consultant to Johnson & Johnson; he has not been paid for any media work.

†P-value is calculated by log-rank test stratified by mutation type (exon 19 deletion or L858R), race (Asian or Non-Asian), and history of brain metastasis (present or absent).