BEERSE, BELGIUM (6 May 2025) – Janssen-Cilag International NV, a Johnson & Johnson company, today announced the submission of an application to the European Medicines Agency (EMA) to extend the RYBREVANT®▼ (amivantamab) marketing authorisation for additional subcutaneous (SC) formulation dosing regimens.
The application seeks approval for the use of an every-three-week (Q3W) SC amivantamab dosing regimen in combination with carboplatin and pemetrexed, for the 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 after failure of prior therapy including an EGFR tyrosine kinase inhibitor (TKI), and for the first-line treatment of adult patients with advanced NSCLC with activating EGFR Exon 20 insertion mutations. Amivantamab is currently approved for intravenous (IV) administration in combination with carboplatin and pemetrexed for these indications.
In addition, the application intends to expand the label to also include an every-four-week (Q4W) SC amivantamab dosing regimen, in combination with LAZCLUZE®▼(lazertinib) for the first-line treatment of adult patients with advanced NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, and as monotherapy for treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy. This follows a recent European Commission approval of an every-two-week (Q2W) SC amivantamab dosing regimen for these indications.4
“Although meaningful progress has been made in the treatment of EGFR-mutated non-small cell lung cancer, significant need remains for treatments with greater convenience while maintaining therapeutic efficacy,” said Henar Hevia, Ph.D., Senior Director, EMEA Therapy Area Head, Oncology, Johnson & Johnson Innovative Medicine. “The subcutaneous formulation of amivantamab reflects our ongoing commitment to innovation, with faster administration and lower rates of infusion-related reactions than IV administration. Pending approval of these additional dosing regimens, subcutaneous amivantamab will benefit eligible patients across all currently approved intravenous amivantamab indications.”
The applications to the EMA are supported by results from the Phase 2 PALOMA-2 study (NCT05498428) and the Phase 1 PALOMA study (NCT04606381), which evaluated the feasibility of SC administration, pharmacokinetics, efficacy and safety of SC amivantamab in multiple regimens in patients with advanced or metastatic EGFR-mutated NSCLC, including the Q3W and Q4W dosing regimens.2,3,5
About PALOMA-2
PALOMA-2 (NCT05498428) is an open-label Phase 2 study evaluating the efficacy, safety, and pharmacokinetics (PK) of first and second-line SC amivantamab (administered via manual injection) as a monotherapy or combined with lazertinib and/or chemotherapy in patients with EGFR-mutated advanced or metastatic NSCLC.3,6 The primary endpoint was objective response rate (ORR) as assessed by the investigator per RECIST v1.1*.3
About PALOMA
PALOMA (NCT04606381), is an open-label, multicentre, dose escalation Phase 1b study which assessed the feasibility of SC administration of amivantamab based on safety and PKs in patients with EGFR-mutated advanced or metastatic NSCLC, and to determine a dose, dose regimen and formulation for SC amivantamab delivery.2,5,7
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.8,9,10,11
The European Commission (EC) has previously approved amivantamab in the following indications:8
Intravenous amivantamab:
- 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.
Subcutaneous amivantamab:
- 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.
Currently, the recommended dose regimen for SC amivantamab for these indications is 1600 mg (2240 mg for body weight ≥80kg) administered weekly from Weeks 1 to 4 (total of four doses), then every two weeks (Q2W) starting at Week 5 onwards.1 When given in combination with lazertinib, it is recommended to administer amivantamab any time after lazertinib when given on the same day.8
The recommended dosing regimen for Q3W SC amivantamab is an initial dose of 1600 mg (2240 mg for body weight ≥80kg) at Week 1 Day 1, followed by 2400mg (3360 mg for body weight ≥80kg) administered weekly from Weeks 2 to 4 (total of three doses), then every three weeks starting at Week 7 onwards.5 For Q4W SC amivantamab, the recommended dosing regimen is 1600 mg (2240 mg for body weight ≥80kg) administered weekly from Weeks 1 to 4 (total of four doses), then 3520 mg (4640mg for body weight ≥80kg) every four weeks starting at Week 5 onwards.5
Subcutaneous amivantamab is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug delivery technology.1
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.8
▼ In line with EU 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 tyrosine kinase inhibitor (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 January 2025, the European Commission approved a marketing authorisation for lazertinib, in combination with amivantamab, for the first-line treatment of adult patients with advanced NSCLC with EGFR exon 19 deletion or exon 21 L858R substitution mutations.13
For a full list of adverse events and information on dosage and administration, contraindications and other precautions when using lazertinib, please refer to the Summary of Product Characteristics.14
▼ In line with EU regulations for new medicines, lazertinib is subject to additional monitoring.
About Non-Small Cell Lung Cancer
In Europe, it is estimated that 484,306 people were diagnosed with lung cancer in 2022.15 NSCLC accounts for 85 percent of all lung cancer cases.16 Lung cancer is Europe’s biggest cancer killer, with more deaths than breast cancer and prostate cancer combined.15
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 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients.18,19,20,21 EGFR ex19del or EGFR exon 21 L858R mutations are the most common EGFR mutations.22 The five-year survival rate for all patients with advanced NSCLC and EGFR mutations treated with EGFR TKIs is less than 20 percent and between 25-32 percent of patients receiving the current first-line standard of care, osimertinib, do not survive long enough to reach second-line treatment.23,24,25,26,27,28,29 EGFR exon 20 insertion (ex20ins) mutations are the third most prevalent activating EGFR mutation.30 Patients with EGFR ex20ins mutations have a real-world five-year OS of eight percent in the frontline setting, which is worse than patients with EGFR ex19del or L858R mutations, who have a real-world five-year OS of 19 percent.24
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://innovativemedicine.jnj.com/emea/. Follow us at https://www.linkedin.com/company/jnj-innovative-medicine-emea/. Janssen-Cilag International NV, Janssen Biotech, Inc. and Janssen-Cilag, S.A. 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 or 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 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, 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. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments.
©Janssen-Cilag International NV 2025. All rights reserved.
*RECIST (v1.1) 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.
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Investor contact:
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CP-516790
May 2025