FDA Approves Simplified Monthly Dosing for RYBREVANT FASPRO™ in EGFR-Mutated NSCLC

Johnson & Johnson recently announced U.S. FDA approval for a simplified monthly dosing schedule of RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj), a subcutaneous therapy, when used with oral LAZCLUZE® (lazertinib) as first-line treatment for adults with epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). This new option allows patients to switch to once-monthly dosing as early as Week 5 after starting bi-weekly doses, delivering the same efficacy and safety as the previous bi-weekly subcutaneous schedule while greatly improving patient convenience by reducing clinic visits.

“This latest milestone represents the culmination of our unwavering efforts to redefine EGFR-mutated NSCLC treatment, building on unmatched overall survival and proactive side effect management to deliver the simplest and fastest monthly combination therapy,” said Mahadi Baig, M.D., M.H.C.M., Vice President, U.S. Medical Affairs, Johnson & Johnson.

Clinical Benefits and Convenience Gains

This approval builds directly on the December 2025 FDA nod for RYBREVANT FASPRO™, which already shortened administration from hours-long intravenous (IV) infusions to mere minutes via subcutaneous injection and cut administration-related reactions (ARRs) by five times compared to IV (from 66% to about 12-13%). With monthly dosing, patients experience even fewer visits, ideal for those managing advanced cancer without losing the therapy’s proven survival advantages from trials like MARIPOSA, which showed superior progression-free survival (PFS) and overall survival (OS) over osimertinib alone.

Experts like Dr. Danny Nguyen from City of Hope highlight how this flexibility helps patients stay on treatment longer, focusing on quality-of-life moments rather than frequent infusions.

Detailed Trial Evidence

Key data come from the PALOMA-2 study (NCT05498428), a Phase 2 trial presented at the 2025 World Conference on Lung Cancer (WCLC). This open-label study tested first-line subcutaneous amivantamab every four weeks (Q4W) plus LAZCLUZE® in EGFR-mutated advanced NSCLC, hitting its primary endpoint of high objective response rate (ORR) per RECIST v1.1, with pharmacokinetics matching historical IV and bi-weekly data. Complementing this, the larger Phase 3 MARIPOSA trial (NCT04487080) enrolled 1,074 patients and demonstrated the combo’s edge: multitargeting EGFR and MET reduced resistance mechanisms like MET amplification (3% vs. 13% on osimertinib) and secondary EGFR mutations (1% vs. 8%), delaying progression and early discontinuations.

In NSCLC, where EGFR mutations drive 10-50% of cases (especially adenocarcinoma) and 5-year survival hovers below 20%, these results address critical unmet needs.​

Safety Profile Overview

Safety with monthly dosing mirrors bi-weekly subcutaneous use, with most adverse events tied to EGFR/MET inhibition think infusion reactions or venous thromboembolic events (VTEs). ARRs occurred in 12% (monthly) vs. 13% (bi-weekly), far below IV’s 66%; VTEs were 13% vs. 11% (with anticoagulation), versus 38% for IV without it.

No new safety signals appeared, plasma levels stayed steady, and only 8% of patients stopped amivantamab due to treatment-related issues, supporting broad tolerability.​

“Monthly dosing offers patients convenience without sacrificing efficacy, with a flexible schedule that reduces time in the clinic, allowing patients to stay on therapy longer and focus on the moments that matter most,” said Danny Nguyen, M.D., Assistant Clinical Professor, Department of Medical Oncology & Therapeutics Research, City of Hope, and principal investigator for the PALOMA-3 and MARIPOSA studies.

RYBREVANT FASPRO™ is a first-in-class bispecific EGFR/MET antibody with immune activity, approved for multiple EGFR-mutated NSCLC settings (exon 19del, L858R, exon 20ins). LAZCLUZE®, a brain-penetrant third-generation EGFR TKI, complements it.

NSCLC accounts for 80-85% of lung cancers worldwide, with EGFR alterations fuelling aggressive growth in non-smokers and younger patients; resistance to single-agent TKIs like osimertinib remains a hurdle, making bispecific approaches like RYBREVANT® transformative.

For complete details on adverse reactions (e.g., ARRs, VTEs), warnings, precautions, and full dosing—especially EGFR/MET-related risks—consult the official RYBREVANT FASPRO™ Prescribing Information or RYBREVANT HCP Site

 Reference

FDA approves RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) as the only EGFR-targeted therapy that can be administered once a month, 17 February 2026, FDA approves RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) as the only EGFR-targeted therapy that can be administered once a month

U.S. FDA Approval of RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) Enables the Simplest, Shortest Administration Time for a First-Line Combination Regimen when combined with LAZCLUZE^® (lazertinib), 17 December 2025, U.S. FDA Approval of RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) Enables the Simplest, Shortest Administration Time for a First-Line Combination Regimen when combined with LAZCLUZE® (lazertinib)

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, Study Details | NCT05498428 | A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer | ClinicalTrials.gov

A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (MARIPOSA), ClinicalTrials.gov ID NCT04487080, Study Details | NCT04487080 | A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer | ClinicalTrials.gov

Prescribing Information, https://www.rybrevanthcp.com/