FDA Approves Subcutaneous Formulation of EGFR-targeted Therapy for Non-small Cell Lung Cancer
Patients now have the option of receiving the bispecific antibody amivantamab as an injection.
The U.S. Food and Drug Administration (FDA) has approved amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) for subcutaneous injection as an alternative for all approved indications of amivantamab-vmjw (Rybrevant), which is administered as an intravenous infusion to treat certain cases of non-small cell lung cancer (NSCLC). Amivantamab and hyaluronidase-lpuj is indicated to treat patients with NSCLC that carries specific mutations in the EGFR gene: exon 19 deletions, exon 21 L858R substitutions, or exon 20 insertions.
Amivantamab and hyaluronidase-lpuj combines a bispecific antibody (amivantamab) with an enzyme (hyaluronidase-lpuj) that makes subcutaneous drug delivery viable by disrupting the extracellular matrix, which could otherwise prevent drug uptake. The bispecific antibody binds to the EGFR and MET proteins expressed on the outside of cells. When the drug binds to its targets, it disrupts the EGFR and MET signaling process that helps drive EGFR-mutant NSCLC. The antibody’s presence on the cell surface also facilitates cell death by attracting immune cells.
The intravenously delivered amivantamab-vmjw is approved as a first-line therapy, in combination with other agents, to treat locally advanced or metastatic NSCLC with certain mutations in the EGFR gene. It is also approved to treat such NSCLC cases if chemotherapy alone has failed to stop disease progression. Because amivantamab and hyaluronidase-lpuj can be administered subcutaneously, rather than as an intravenous infusion, to treat these cancers, the new approval gives patients a more convenient treatment option.
The approval was based on results from the randomized, open-label, multicenter, phase III PALOMA-3 clinical trial, which analyzed the safety and efficacy of amivantamab and hyaluronidase-lpuj in patients with locally advanced or metastatic NSCLC that had either an exon 19 deletion or an exon 21 L858R substitution mutation in the EGFR gene. The 418 enrolled patients were randomly assigned 1:1 to receive lazertinib (Lazcluze) with either intravenous amivantamab-vmjw or subcutaneous amivantamab and hyaluronidase-lpuj. No significant detriments to pharmacokinetics, objective response rate, progression-free survival, or overall survival were observed between the intravenous arm and the subcutaneous arm.
The recommended dosing schedule for subcutaneous amivantamab and hyaluronidase-lpuj varies, depending on both patients’ body weight and the specific indication. But for all uses, amivantamab and hyaluronidase-lpuj should be initially administered at a ratio of 8 mg of amivantamab to 100 units of hyaluronidase, and the dose may be modified or treatment stopped if disease progression or unacceptable toxicity occurs.
NSCLC is the most common form of lung cancer, accounting for more than 80% of U.S. lung cancer cases. In metastatic lung cancer, mutations in the EGFR gene are the second most common cancer-causing mutations. According to federal statistics, it was estimated that 226,650 individuals would be diagnosed with lung cancer and 124,730 patients would die of the disease in the United States in 2025.
The FDA rendered its decision on December 17, 2025. Check this resource for updated information on all therapeutics regulated by the FDA.