FDA OKs Subcutaneous Amivantamab in EGFR+ NSCLC

The FDA has approved subcutaneous amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) as a treatment for patients with non–small cell lung cancer (NSCLC) harboring EGFR mutations, according to a press release from the developer, Johnson & Johnson.¹ The agency approved the subcutaneous formulation for all indications for which intravenous amivantamab (Rybrevant) has already received approval.

According to the press release, subcutaneous amivantamab, when administered with lazertinib (Lazcluze), may significantly reduce administration time from several hours with the intravenous formulation to 5 minutes. Additionally, the subcutaneous agent has shown an approximately 5-fold reduction in administration-related reactions vs the intravenous agent while reducing the frequency of venous thromboembolism.

Other supporting data for the approval came from the phase 3 PALOMA-3 trial (NCT05388669), in which investigators assessed the pharmacokinetics, efficacy, and safety of subcutaneous amivantamab vs its intravenous formulation among 418 patients with EGFR-mutated NSCLC. Investigators previously presented data from the PALOMA-3 trial at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.²

Of note, findings from PALOMA-3 showed that duration of response (DOR), progression-free survival (PFS), and overall survival (OS) improved with subcutaneous amivantamab plus lazertinib compared with intravenous amivantamab. The 12-month OS rates were 65% with subcutaneous treatment vs 51% with intravenous therapy (HR, 0.62; 95% CI, 0.42-0.92; P = .02).

"The combination of [amivantamab] plus [lazertinib] changes the biology of the disease by preventing resistance and delivers unmatched [OS] in the first-line setting, while omitting chemotherapy from treatment. Now, with the approval of [subcutaneous amivantamab], we have an entirely new subcutaneous therapy that offers consistent results compared to intravenous delivery, while providing a more patient-centered experience," PALOMA-3 principal investigator Danny Nguyen, MD, assistant clinical professor in the Department of Medical Oncology & Therapeutics Research at City of Hope, stated in the press release.¹

In the subcutaneous and intravenous amivantamab arms, respectively, 13% vs 66% of patients had administration-related reactions; 11% vs 18% from each arm had venous thromboembolism. The most common toxicities associated with subcutaneous amivantamab plus lazertinib in the PALOMA-3 trial included pain, rash, nail toxicity, edema, nausea, musculoskeletal pain, and peripheral neuropathy.

"Patients now have a simple, chemotherapy-free frontline option that not only targets the disease more precisely but also significantly improves survival. With the introduction of [subcutaneous amivantamab], care becomes faster, less invasive, and more aligned with what matters most to patients: time, comfort, and dignity," Joelle Fathi, DNP, chief healthcare delivery officer at GO2 for Lung Cancer, stated in the press release.¹ "This therapy reduces the physical and emotional burden of lengthy infusions, giving patients and their families the opportunity to reclaim precious moments and focus on living, rather than treatment."

The coprimary end points of the PALOMA-3 trial were trough concentration on cycle 2, day 1 or cycle 4, day 1 and area under the curve on cycle 2. Key secondary end points included ORR and PFS, with OS included as a predefined exploratory end point.

References

1. 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). News release. Johnson & Johnson. December 17, 2025. Accessed December 17, 2025. https://tinyurl.com/2wt6j6be
2. Leighl NB, Akamatsu H, Lim SM, et al. Subcutaneous versus intravenous amivantamab, both in combination With lazertinib, in refractory rpidermal growth factor receptor-mutated non-small cell lung cancer: primary results from the phase III PALOMA-3 study. J Clin Oncol. 2024;42(30):3593-3605. doi: 10.1200/JCO.24.01001.