FDA Approves Monthly Subcutaneous Amivantamab Dosing for EGFR-Mutated NSCLC

The Food and Drug Administration (FDA) has approved a monthly dosing schedule for Rybrevant Faspro for the treatment of epidermal growth factor receptor (EGFR)-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). The approval makes Rybrevant Faspro the only EGFR-targeted therapy that can be administered once a month.

Rybrevant Faspro is a subcutaneous co-formulation of amivantamab, a bispecific EGFR-directed and MET receptor-directed antibody, and hyaluronidase, an endoglycosidase. The approval of the monthly dosing regimen was based on data from cohort 5 of the open-label phase 2 PALOMA-2 trial (ClinicalTrials.gov Identifier: NCT05498428).

Treatment-naïve study participants with EGFR Ex19del or L858R mutations (N=77) were administered Rybrevant Faspro 1600mg weekly for the first 4 weeks, followed by a maintenance dose of 3520mg every 4 weeks, alongside lazertinib 240mg daily. The primary endpoint was overall response rate (ORR) based on investigator assessment.

Findings showed at a median follow-up of 6.5 months, the ORR was 82% (95% CI, 71-90) based on investigator assessment and 87% (95% CI, 77-94) based on independent central review (secondary endpoint). These results were comparable to that of the MARIPOSA study, which demonstrated an ORR of 86% (95% CI, 83-89) with a biweekly dosing regimen of intravenous (IV) amivantamab plus lazertinib.

The safety profile of the monthly dosing regimen of subcutaneous amivantamab was similar to that of the biweekly subcutaneous dosing schedule. Administration related reactions were consistent across both subcutaneous dosing schedules and significantly lower versus IV administration (12% with monthly dosing vs 13% with biweekly dosing vs 66% with IV dosing).

Additionally, the incidence of venous thromboembolic events with the monthly subcutaneous dosing schedule was comparable with biweekly subcutaneous dosing (both given alongside anticoagulation) and lower than IV administration without anticoagulation (13% with monthly dosing vs 11% with biweekly dosing vs 38% with IV dosing). No new safety signals were identified.

The mean plasma concentration levels were similar when compared with IV and biweekly subcutaneous dosing administration.

Under the updated labeling, adult patients on biweekly IV amivantamab or subcutaneous Rybrevant Faspro may now transition to a monthly subcutaneous schedule starting on or after week 5. This modification is expected to simplify care delivery and improve patient convenience.

Rybrevant Faspro is supplied as a solution in a single-dose vial in 4 dosage strengths: amivantamab 1600mg and hyaluronidase 20,000 units per 10mL; amivantamab 2240mg and hyaluronidase 28,000 units per 14mL; amivantamab 2400mg and hyaluronidase 30,000 units per 15mL; and amivantamab 3520mg and hyaluronidase 44000 units per 22mL.