Amivantamab and hyaluronidase-lpuj (Rybrevant Faspro, Johnson & Johnson) is now approved as a once-monthly subcutaneous injection for the first-line treatment of epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC).

The agent was first approved in December 2025 for the same indication but with a biweekly dosing schedule, based on findings from the PALOMA-3 trial, as reported by Medscape Medical News.

FDA approval of the new, simplified dosing schedule was based on findings from the PALOMA-2 trial showing that monthly injections in combination with lazertinib (Lazcluze, Johnson & Johnson) delivered high objective response rates — 82% and 87% by investigator and independent central review, respectively — in previously untreated EGFR-mutated advanced NSCLC.

Findings from PALOMA-2, as presented at the 2025 World Conference on Lung Cancer, also showed a significant reduction in administration-related reactions (ARRs) when compared with rates seen historically with intravenous (IV) administration and comparable ARRs to those seen with biweekly subcutaneous injections, Johnson & Johnson stated in a press release announcing the new approval.

“This milestone builds upon the recent FDA approval of Rybrevant Faspro, which transformed administration time from hours to minutes and offers a fivefold reduction in ARRs, when compared with IV delivery,” the company noted. “With this newly approved monthly dosing schedule, patients are able to transition to monthly dosing as early as Week 5.”

PALOMA-2 showed that the safety profile of monthly dosing is comparable to that seen with biweekly dosing. Most adverse events were related to EGFR/MET oncogene inhibition.

ARRs with monthly vs biweekly dosing were 12% and 13%, respectively, and were fivefold lower vs historical data for IV administration, the company stated, noting that venous thromboembolic events were also consistent with biweekly dosing (13% vs 11%, respectively, with anticoagulation) and lower than historic IV data without anticoagulation. No new safety signals were observed in PALOMA-2, and only 8% of patients discontinued injections due to treatment-related adverse events. 

Mean plasma concentrations were also consistent with IV and biweekly subcutaneous dosing, suggesting pharmacokinetic comparability across the dosing regimens.

“A monthly dosing schedule offers patients convenience without sacrificing efficacy, Danny Nguyen, MD, of City of Hope, Duarte, California, and principle investigator for PALOMA-3, stated in the press 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.”

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.com or on X: @SW_MedReporter.