Flexible SC Amivantamab Regimens Now Authorized EU-Wide for EGFR-Mutant Lung Cancer

Johnson & Johnson announced that the European Commission has approved an extension of the RYBREVANT (amivantamab) marketing authorisation to include additional subcutaneous (SC) dosing regimens. This decision now authorises SC amivantamab across all previously approved intravenous (IV) indications for advanced non-small cell lung cancer (NSCLC) with specific EGFR mutations.

Henar Hevia, Ph.D., Senior Director, EMEA Therapeutic Area Head, Oncology, Johnson & Johnson Innovative Medicine, highlighted this as a commitment to easing treatment burden while preserving efficacy across indications, prioritising patient experience.​

New SC Dosing Regimens

The approval introduces two flexible SC options.

• Every-four-week (Q4W) SC amivantamab: Used in combination with LAZCLUZE (lazertinib) for first-line treatment of adult patients with advanced NSCLC harbouring EGFR exon 19 deletions or exon 21 L858R substitution mutations. Also approved as monotherapy for advanced NSCLC with activating EGFR exon 20 insertion mutations after platinum-based therapy failure.​
• Every-three-week (Q3W) SC amivantamab: Combined with carboplatin and pemetrexed for advanced NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations after prior therapy failure, including EGFR tyrosine kinase inhibitors (TKIs). Also, for first-line treatment of EGFR exon 20 insertion mutations.

These regimens allow transition from every-two-week dosing, aligning better with patient needs while maintaining efficacy and safety comparable to IV formulations.​

Supporting Clinical Evidence

Data from Phase 2 PALOMA-2 and Phase 1 PALOMA studies supported the approval. These trials evaluated SC amivantamab’s feasibility, pharmacokinetics, efficacy, and safety in EGFR-mutated advanced or metastatic NSCLC patients across Q3W and Q4W regimens.

SC administration showed response rates and safety profiles consistent with IV dosing but with fewer administration-related reactions. Infusion time dropped to about five minutes versus five hours for the first IV dose. Common treatment-emergent adverse events mirrored IV experiences, including EGFR- and MET-related issues like dermatitis acneiform, paronychia, rash, stomatitis, and hypoalbuminemia.

Study Overviews

PALOMA (NCT04606381): An open-label, multicentre Phase 1b dose-escalation study assessing SC amivantamab safety and pharmacokinetics in advanced solid tumours suitable for EGFR- or MET-directed therapy. It identified optimal SC dosing, regimen, and formulation.

PALOMA-2 (NCT05498428): An open-label Phase 2 study examining SC amivantamab (manual injection) as monotherapy or with lazertinib and/or chemotherapy in first- and second-line EGFR-mutated locally advanced or metastatic NSCLC. Primary endpoints included safety and investigator-assessed objective response rate per RECIST v1.1.​

About Amivantamab and Prior Approvals

Amivantamab is a fully human EGFR-MET bispecific antibody targeting tumours with activating and resistant EGFR mutations, MET alterations, and immune system engagement. It is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20) using Halozyme’s ENHANZE drug delivery technology for SC use.

Previously approved IV indications include combinations with lazertinib (first-line EGFR exon 19del/L858R), carboplatin-pemetrexed (post-TKI exon 19del/L858R or first-line exon 20ins), and monotherapy (post-platinum exon 20ins). SC was earlier approved for lazertinib combo (first-line exon 19del/L858R) and monotherapy (post-platinum exon 20ins).

Silvia Novello, M.D., Ph.D., Professor of Medical Oncology at San Luigi Hospital, University of Turin, Italy, noted that additional SC options advance clinical practice by offering flexibility, reduced clinic time, and fewer reactions for EGFR-mutated NSCLC patients and healthcare teams.

About LAZCLUZE (Lazertinib)

Lazertinib, licensed from Yuhan Corporation, is an oral, third-generation, brain-penetrant EGFR TKI targeting T790M and activating mutations while sparing wild-type EGFR. Approved by the EC in January 2025 with amivantamab for first-line advanced NSCLC with EGFR exon 19del or L858R mutations.​

NSCLC

In Europe, lung cancer affected about 484,306 people in 2022, with NSCLC comprising 85% of cases, Europe’s leading cancer killer. EGFR mutations occur in 10-15% of Western adenocarcinoma patients and 40-50% of Asian patients, with exon 19del/L858R most common and exon 20ins third-most prevalent.

Five-year survival remains poor: <20% for advanced EGFR-mutated NSCLC on TKIs; frontline exon 20ins at 8% versus 19% for common mutations.​

For full adverse events, dosing, and precautions, consult the RYBREVANT and LAZCLUZE Summaries of Product Characteristics on the EMA website. Both drugs are under additional EU monitoring for new medicines.

 Reference

Subcutaneous RYBREVANT^®▼ (amivantamab) approved by European Commission for every-three-week and every-four-week dosing for patients with advanced EGFR-mutated non-small cell lung cancer, 23 February 2026, Subcutaneous RYBREVANT®▼ (amivantamab) approved by European Commission for every-three-week and every-four-week dosing for patients with advanced EGFR-mutated non-small cell lung cancer

A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (PALOMA-2), ClinicalTrials.gov ID NCT05498428, https://clinicaltrials.gov/study/NCT05498428

A Study of Amivantamab Subcutaneous (SC) Administration for the Treatment of Advanced Solid Malignancies (PALOMA), ClinicalTrials.gov ID NCT04606381, https://clinicaltrials.gov/study/NCT04606381

Rybrevant, Summary of Product Characteristics, Rybrevant, INN-amivantamab