FDA approves once-monthly subcutaneous amivantamab dosing in EGFR-mutated NSCLC
The FDA approved once-monthly subcutaneous amivantamab with lazertinib for first-line EGFR-mutated advanced NSCLC. PALOMA-2 showed high response rates and no new safety signals.
The U.S. Food and Drug Administration on February 17, 2026 approved a new simplified once-monthly dosing schedule for RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj) when administered in combination with oral lazertinib for first-line treatment of EGFR-mutated advanced non-small cell lung cancer. Patients may transition to monthly dosing as early as Week 5, with clinical outcomes consistent with the previously approved bi-weekly subcutaneous regimen.
The approval follows the December 17, 2025 FDA approval of RYBREVANT FASPRO across all FDA-approved indications of RYBREVANT (amivantamab-vmjw), establishing the first and only subcutaneous formulation of amivantamab for patients with EGFR-mutated NSCLC and enabling a transition from prolonged intravenous infusion to rapid subcutaneous administration.
The updated schedule was supported by findings from the Phase 2 PALOMA-2 study. As of the October 24, 2024 data cutoff, 77 participants in cohort 5 received subcutaneous amivantamab coformulated with hyaluronidase via abdominal injection. Dosing was administered weekly during the first 4 weeks, followed by once-every-4-weeks maintenance dosing, while lazertinib 240 mg was administered orally once daily.
The investigator-assessed objective response rate was 82% (95% CI, 71%-90%), and independent central review reported an objective response rate of 87% (95% CI, 77%-94%). The median time to response was 8.1 weeks (range, 7.0-16.5). Although the median duration of response, progression-free survival, and overall survival were not yet estimable at the time of data cutoff, 87% of participants remained on treatment at 6.5 months of follow-up.
Administration-related reactions occurred in 12% of participants, with only 1 grade 3 or higher event. The monthly regimen showed comparable safety to bi-weekly subcutaneous dosing, consistent pharmacokinetic exposure, and no new safety signals were identified. Clinical outcomes were reported as consistent with the previously approved bi-weekly subcutaneous regimen.
The initial subcutaneous approval was supported by the Phase 3 PALOMA-3 trial, which enrolled 418 patients with EGFR-mutated advanced or metastatic NSCLC following progression on osimertinib and platinum-based chemotherapy. The trial met both co-primary pharmacokinetic endpoints, demonstrating comparable amivantamab exposure between subcutaneous and intravenous formulations based on Ctrough and AUC parameters. Median overall survival favored the subcutaneous arm (HR 0.62; 95% CI, 0.42-0.92; nominal P = 0.02), with 12-month survival rates of 65% versus 51% for subcutaneous versus intravenous administration.
In the Phase 3 MARIPOSA trial, amivantamab plus lazertinib versus osimertinib in the first-line treatment of advanced NSCLC harboring EGFR exon 19 deletions or L858R mutations showed a statistically significant overall survival benefit at a median follow-up of 37.8 months, with HR 0.75 (95% CI, 0.61-0.92; P = 0.0048), median overall survival not reached in the combination arm, and median overall survival of 36.7 months with osimertinib.