FDA Approves Amivantamab and Hyaluronidase-lpuj, Revolutionizing Lung Cancer Treatment With 5-Minute Subcutaneous Delivery

In a significant advance for cancer care, the FDA has approved amivantamab and hyaluronidase-lpuj (Rybrevant Faspro; Johnson & Johnson), marking the first and only subcutaneous (SC) administered therapy for patients with epidermal growth factor receptor (EGFR)-mutated non–small cell lung cancer (NSCLC).¹

The approval dramatically streamlines the treatment process, reducing administrative time from several hours to as little as 5 minutes. This new SC formulation is approved across all existing indications for intravenous (IV) amivantamab-vmjw.¹

“Patients now have a simple, chemotherapy-free frontline option that not only targets the disease more precisely but also significantly improves survival,” said Joelle Fathi, DNP, chief healthcare delivery officer at GO2 for Lung Cancer, in a news release. “With the introduction of Rybrevant Faspro, care becomes faster, less invasive, and more aligned with what matters most to patients: time, comfort, and dignity. 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.”¹

Faster Care, Fewer Reactions

The approval is based on results from the phase 3 PALOMA-3 study (NCT05388669), which compared the SC formulation of amivantamab combined with oral lazertinib (Lazcluze; Johnson & Johnson) against the IV formulation plus lazertinib. The SC regimen demonstrated substantial patient convenience and a reduced burden on health care resources.²

“The approval of Rybrevant Faspro is a pivotal step forward, as EGFR+ NSCLC patients have previously faced limited treatment options,” said Biljana Naumovic, president of solid tumors at Johnson & Johnson Innovative Medicine, in a news release. “Now, patients are gaining greater access to this transformative treatment, as well as the tools needed to proactively manage common dermatological effects.”¹

Crucially, the new SC delivery method resulted in an approximately 5-fold reduction in administration-related reactions (ARRs) compared to IV administration (13% in the SC arm vs 66% in the IV arm). These reactions were primarily grade 1 or 2.² The SC arm also showed a lower incidence of venous thromboembolism (VTE) events (11% vs 18% for IV). Prophylactic anticoagulation is recommended for the first 4 months of treatment and was shown to safely reduce VTE risk across both arms in the PALOMA-3 study.²

Unexpected Survival Trends

The PALOMA-3 study met its coprimary goals of demonstrating noninferior pharmacokinetics (PK) and objective response rate (ORR) compared to the IV arm, and researchers observed unexpected benefits with subcutaneous delivery.

Data presented at the American Society of Clinical Oncology 2024 meeting revealed that the SC arm showed longer duration of response (DoR), improved progression-free survival (PFS), and notably longer overall survival (OS) compared to the IV arm.¹ At a 12-month follow-up, 65% of patients receiving the SC regimen were alive compared with 51% treated with the IV regimen.^1,2

Building on Unmatched Overall Survival

Amivantamab plus hyaluronidase-lpuj is indicated in combination with lazertinib for the first-line treatment of adults with locally advanced or metastatic NSCLC driven by EGFR exon 19 deletions or L858R substitution mutations.¹

This SC approval reinforces the effectiveness of the amivantamab plus lazertinib regimen, which previously demonstrated a statistically significant and clinically meaningful OS benefit in the phase 3 MARIPOSA study (NCT04487080). The regimen, projected to exceed 4 years of OS, works through a triple mode of action by targeting EGFR mutations from 2 angles, blocking MET, and engaging the immune system. This approach aims to change the natural history of the disease by reducing the spectrum and complexity of acquired resistance mechanisms, such as MET amplifications and secondary EGFR mutations.¹

“The combination of Rybrevant plus Lazcluze changes the biology of the disease by preventing resistance and delivers unmatched overall survival in the first-line setting, while omitting chemotherapy from treatment,” said Danny Nguyen, MD, assistant clinical professor in the department of medical oncology and therapeutics research at City of Hope, and principal investigator of the PALOMA-3 and MARIPOSA studies, in a news release. “Now, with the approval of Rybrevant Faspro, we have an entirely new subcutaneous therapy that offers consistent results compared to intravenous delivery, while providing a more patient-centered experience.”

REFERENCES

1. US 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 18, 2025. https://www.jnj.com/media-center/press-releases/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

2. Leighl NB, Akamatsu H, Lim SM, et al. Subcutaneous amivantamab vs intravenous amivantamab, both in combination with lazertinib, in refractory EGFR-mutated, advanced non-small cell lung cancer (NSCLC): primary results, including overall survival (OS), from the global, phase 3, randomized controlled PALOMA-3 trial. J Clin Oncol. 2024;42(suppl_17). doi:10.1200/JCO.2024.42.17_suppl.LBA8505