FDA Approves Subcutaneous Formulation of Amivantamab and Hyaluronidase-lpuj
Key Clinical Summary
- Population and Design: On December 17, 2025, the US FDA approved subcutaneous amivantamab + hyaluronidase-lpuj for all adult indications of the IV formulation, based on the phase 3 PALOMA-3 trial (NCT05498428) in 418 patients with EGFR exon 19 deletion or exon 21 L858R–mutated NSCLC, randomized to subcutaneous vs IV amivantamab + lazertinib.
- Efficacy: Pharmacokinetic equivalence achieved—Cycle 2 AUC GMR 1.03 (95% CI, 0.98 to 1.09) and steady-state Ctrough GMR 1.43 (95% CI, 1.27 to1.61); no clinically meaningful differences in ORR, PFS, or OS between formulations.
- Safety: Comparable safety profiles; markedly lower administration-related reaction rate (13% SC vs 66% IV). Label warnings include hypersensitivity, pneumonitis, VTEs, dermatologic and ocular AEs, and embryo-fetal toxicity. Approval supports a more convenient, lower-reactivity SC option across all amivantamab indications.
On December 17, 2025, amivantamab and hyaluronidase-lpuj for subcutaneous injection was approved by the US Food and Drug Administration (FDA) for adult patients across all indications previously approved for the intravenous (IV) formulation of amivantamab.
This approval was based on results from the PALOMA-3 study (NCT05498428), a randomized, open-label, multicenter, multiregional trial that enrolled 418 adults with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations.
Patients were randomized 1:1 to receive either subcutaneous amivantamab and hyaluronidase-lpuj plus lazertinib or intravenous amivantamab plus lazertinib. The primary pharmacokinetic end points were trough concentration at steady state (Ctrough) and area under the curve (AUC).
At the recommended every 2-week dosage, the geometric mean ratio (GMR) for Cycle 2 AUC (Day 1 to 15) was 1.03 (95% confidence interval [CI], 0.98 to 1.09), and steady-state Ctrough on Cycle 4 Day 1 was 1.43 (95% CI, 1.27 to 1.61). For every 3-week regimen, simulated GMRs were 1.20 (95% CI, 1.15 to 1.26) for average concentration across Cycle 2 and 1.32 (1.23 to 1.42) for steady-state Ctrough.
No clinically meaningful differences were observed between subcutaneous and intravenous formulations in overall response rate (ORR), progression-free survival (PFS), or overall survival (OS).
The safety profile of subcutaneous amivantamab was comparable to that of intravenous amivantamab, except for a lower incidence of administration-related reactions (ARRs) which included 13% for subcutaneous administration and 66% infusion-related reactions (IRRs) for the intravenous formulation.
The prescribing information includes warnings and precautions for hypersensitivity and administration-related reactions, interstitial lung disease/pneumonitis, venous thromboembolic events, dermatologic adverse reactions, ocular toxicity, and embryo-fetal toxicity.
The recommended dosage of subcutaneous amivantamab varies by baseline body weight and indication.
Source:
US Food and Drug Administration. FDA approves amivantamab and hyaluronidase-lpuj for subcutaneous injection. Accessed December 18, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-amivantamab-and-hyaluronidase-lpuj-subcutaneous-injection
