FDA Approves Subcutaneous Amivantamab Monthly Dosing in EGFR+ NSCLC

The FDA has approved a simplified monthly dosing schedule for the subcutaneous formulation of amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) when used in combination with oral lazertinib (Lazcluze) for the first-line treatment of adult patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations, according to a news release from Johnson & Johnson, the drug’s developer.

Recommended Dosing and Administration

The newly approved regimen allows patients to transition to a monthly (every 4 weeks) dosing schedule starting at week 5. For the initial 4 weeks of treatment, the medication is administered via weekly subcutaneous injections. This update builds upon the previous FDA approval of the subcutaneous formulation in December, which significantly reduced administration time from several hours to just a few minutes compared with intravenous (IV) delivery. According to clinical data, the monthly schedule delivers consistent outcomes and pharmacokinetic comparability to the previously established biweekly subcutaneous dosing.

Clinical Efficacy: The PALOMA-2 Study

The approval is supported by findings from the phase 2 PALOMA-2 trial (NCT05498428), which evaluated the efficacy, safety, and pharmacokinetics of first-line subcutaneous amivantamab in various combinations for EGFR-mutated advanced NSCLC. Data from cohort 5 of the trial, presented at the 2025 International Association for the Study of Lung Cancer World Conference on Lung Cancer, demonstrated that monthly amivantamab plus lazertinib achieved a high objective response rate, which was the primary end point.

Principal investigator Danny Nguyen, MD, noted in the announcement that the flexible schedule reduces clinic time, potentially allowing patients to remain on therapy longer. The study also confirmed that mean plasma concentration levels for the once-monthly regimen were consistent with historical data from both IV and biweekly subcutaneous administration.

Safety and Nursing Considerations

The safety profile of the once-monthly subcutaneous dosing schedule was found to be comparable to the biweekly subcutaneous schedule. In the phase 3 PALOMA-3 trial (NCT05388669), all-grade administration-related reactions (ARRs) occurred in 13% of patients, with 89% of these occurring during the initial dose at week 1, a reduction by 5 times in ARRs compared with historical IV administration rates of 66%, according to the release.

Oncology nurses and advanced practice providers should be aware of the following management protocols:

• Premedication: Patients should be premedicated with antihistamines, antipyretics, and glucocorticoids prior to administration to mitigate the risk of ARRs.
• Monitoring: The median time to ARR onset is approximately 2 hours; patients should be monitored in a setting equipped with cardiopulmonary resuscitation resources.
• Venous thromboembolic (VTE) prophylaxis: Serious VTE events, including pulmonary embolism, have been reported. Prophylactic anticoagulation is recommended for the first 4 months of treatment.

In the PALOMA-3 study, the most frequent adverse events (AEs) reported in 20% or more of patients included rash (80%), nail toxicity (58%), musculoskeletal pain (50%), fatigue (37%), stomatitis (36%), edema (34%), nausea (30%), and gastrointestinal disturbances such as diarrhea, vomiting, and constipation, each occurring in 22% of patients.

Significant grade 3 or 4 laboratory abnormalities included decreased lymphocyte counts (6%), decreased sodium levels (5%), and decreased potassium levels (5%). While these reactions are frequent, data indicate that the safety profile for monthly dosing is comparable to biweekly administration, and only 8% of patients discontinued amivantamab due to treatment-related AEs.

Mechanism of Action and Guidelines

Amivantamab is a first-in-class, fully human bispecific antibody that targets both EGFR and MET while engaging immune cell-directing activity. The combination with lazertinib addresses common resistance mechanisms, such as MET amplification, which often limits the long-term efficacy of third-generation tyrosine kinase inhibitors. The National Comprehensive Cancer Network currently includes amivantamab-based regimens as a category 1 preferred option for the first-line treatment of patients with EGFR exon 19 deletions or L858R mutations.

Reference

FDA approves Rybrevant Faspro (amivantamab and hyaluronidase-lpuj) as the only EGFR-targeted therapy that can be administered once a month. News release. Johnson & Johnson. February 17, 2026. Accessed February 17, 2026. https://www.prnewswire.com/news-releases/fda-approves-rybrevant-faspro-amivantamab-and-hyaluronidase-lpuj-as-the-only-egfr-targeted-therapy-that-can-be-administered-once-a-month-302689494.html