FDA Approves Monthly First-Line Amivantamab and Hyaluronidase Dosing for EGFR-Mutated, Advanced NSCLC

The FDA has approved a simplified monthly dosing schedule of amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) for the first-line treatment of patients with EGFR-mutated, advanced non–small cell lung cancer (NSCLC).¹

This regulatory decision builds on the December 2025 FDA approval of subcutaneous first-line amivantamab and hyaluronidase, which was approved across all current indications for amivantamab-vmjw (Rybrevant), based on findings from the phase 3 PALOMA-3 trial (NCT05388669).²

Data from the phase 2 PALOMA-2 trial (NCT05498428) showed that when given in combination with oral lazertinib (Lazcluze), amivantamab and hyaluronidase dosed monthly produced efficacy outcomes consistent with those seen with the previously approved subcutaneous dosing schedule—once weekly for the first 4 weeks and every 2 weeks thereafter, as well as the intravenous (IV) formulation of amivantamab.^1,3,4 With the current monthly dosing schedule, patients can transition to monthly dosing at week 5 at the earliest.¹

“A monthly dosing schedule offers patients convenience without sacrificing efficacy,” Danny Nguyen, MD, assistant clinical professor in the Department of Medical Oncology and Therapeutics Research at City of Hope in Duarte, California, and principal investigator for the pivotal PALOMA-3 and phase 3 MARIPOSA (NCT04487080) studies, stated in a news release. “With a flexible schedule that reduces time in the clinic, patients may be able to stay on therapy longer and free up time to focus on the moments that matter most.”

Findings from MARIPOSA supported the FDA approval of IV first-line amivantamab plus lazertinib for the treatment of patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.⁵

What were the key findings from PALOMA-2 with amivantamab and hyaluronidase plus lazertinib in NSCLC?

Data from the PALOMA-2 trial, presented at the 2025 World Conference on Lung Cancer, showed that every-4-weeks dosing of amivantamab and hyaluronidase in combination with lazertinib yielded an investigator-assessed overall response rate (ORR) of 82% and an Independent Central Review–assessed ORR of 87% in patients with previously untreated, EGFR-mutated, advanced NSCLC (n = 77).⁴ The confirmed ORRs per these respective groups were 79% and 83%. The median time to response was 8.1 weeks. At a median follow-up of 6.5 months, the median durations of response, progression-free survival, and overall survival (OS) were not reached.

The trial data also demonstrated a significant reduction in the rate of administration-related reactions (ARRs) with the subcutaneous formulation vs the IV administration.¹ The rate of ARRs was 12%, and only one grade 3 or higher ARR was reported.⁴ Conversely, historical data showed that the ARR rates were 13% with every-2-weeks subcutaneous dosing and 66% with IV dosing.¹ Additionally, the rate of venous thromboembolic events (VTEs) with every-4-weeks subcutaneous dosing was 13% with anticoagulation compared with 11% with every-2-weeks subcutaneous dosing with anticoagulation. The historical rate of VTEs with IV amivantamab without anticoagulation was 38%.

Overall, no new safety signals were identified with the every-4-weeks subcutaneous formulation.^1,4 Additionally, the mean plasma concentration levels of this formulation and dosing schedule were consistent with historical data with the IV and every-2-weeks subcutaneous amivantamab dosing, showing that the regimens have pharmacokinetic equivalency. In the every-4-weeks population, 8% of patients discontinued amivantamab treatment due to treatment-related adverse effects (AEs).

“This latest milestone represents the culmination of our unwavering efforts and commitment to fundamentally redefine the way we treat patients with EGFR-mutated NSCLC,” Mahadi Baig, MD, MHCM, vice president of US medical affairs at Johnson & Johnson, added in the company news release.¹ “Building on unmatched OS and regimens that support proactive AE management, this once-monthly injection now delivers the simplest and fastest combination therapy for patients with EGFR-mutated NSCLC.”

References

1. 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.investor.jnj.com/investor-news/news-details/2026/FDA-approves-RYBREVANT-FASPRO-amivantamab-and-hyaluronidase-lpuj-as-the-only-EGFR-targeted-therapy-that-can-be-administered-once-a-month/default.aspx
2. 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 February 17, 2026. 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
3. 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):LBA8505. doi:10.1200/JCO.2024.42.17_suppl.LBA8505
4. PALOMA-2 study: subcutaneous amivantamab every 4 weeks plus lazertinib shows high response rate in EGFR-mutated NSCLC. News release. International Association for the Study of Lung Cancer. September 9, 2025. Accessed February 17, 2026. https://www.iaslc.org/iaslc-news/press-release/paloma-2-study-subcutaneous-amivantamab-every-4-weeks-plus-lazertinib
5. Rybrevant (amivantamab-vmjw) plus Lazcluze (lazertinib) approved in the US as a first-line chemotherapy-free treatment for patients with EGFR-mutated advanced lung cancer. News release. Johnson & Johnson. August 20, 2024. Accessed February 17, 2026. https://www.jnj.com/media-center/press-releases/rybrevant-amivantamab-vmjw-plus-lazcluze-lazertinib-approved-in-the-u-s-as-a-first-line-chemotherapy-free-treatment-for-patients-with-egfr-mutated-advanced-lung-cancer