On December 17, 2025, the Food and Drug Administration approved amivantamab and hyaluronidase-lpuj (Rybrevant Faspro, Janssen Biotech, Inc.) for subcutaneous injection for adult patients across all indications approved for the intravenous formulation of amivantamab (Rybrevant, Janssen Biotech, Inc.). See the prescribing information for the specific indications.
Full prescribing information for Rybrevant Faspro will be posted on Drugs@FDA.
Safety and Efficacy
The subcutaneous injection of amivantamab and hyaluronidase-lpuj was evaluated in PALOMA-3, a randomized, open-label, multicenter, multiregional trial in adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR-exon 19 deletions or exon 21 L858R substitution mutations. A total of 418 patients were randomized (1:1) to receive either subcutaneous amivantamab and hyaluronidase-lpuj plus lazertinib or intravenous amivantamab plus lazertinib.
The primary outcome measures were trough concentrations at steady state (Ctrough were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). At the recommended every two-week dosage, the observed geometric mean ratio (GMR) (90% CI) for Cycle 2 AUCDay 1-Day15 was 1.03 (0.98, 1.09) and for steady-state Ctrough on Cycle 4 Day 1 was 1.43 (1.27, 1.61). For the recommended every three-week dosage, the simulated GMRs (90% CI) for the average concentration of Cycle 2 Day 1 to Day 21 was 1.20 (1.15, 1.26) and for steady-state Ctrough was 1.32 (1.23, 1.42), with the lower limits of the GMRs (90% CI) also above the pre-specified threshold of 0.8 for comparability.
There were no notable differences in descriptive analyses of ORR and PFS, and no evidence of a potential detrimental effect on OS, observed in patients who received subcutaneous amivantamab compared to patients who received intravenous amivantamab.
The safety profile of the subcutaneous amivantamab arm was generally similar to the safety profile of the intravenous amivantamab IV arm in PALOMA-3. One exception is that the incidence of systemic administration reactions (ARRs) for subcutaneous amivantamab SC was lower than the incidence of infusion related reactions (IRRs) for intravenous amivantamab. The incidence of systemic ARRs of any grade was 13% for subcutaneous amivantamab compared to 66% IRRs for intravenous amivantamab.
The prescribing information includes warnings and precautions for hypersensitivity and administration-related reactions, interstitial lung disease/pneumonitis, venous thromboembolic events with concomitant use with lazertinib, dermatologic adverse reactions, ocular toxicity, and embryo-fetal toxicity.
The recommended dosage of subcutaneous amivantamab is based on baseline bodyweight and depends on the specific indication. See the prescribing information for specific dosage information.
Expedited Programs
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with Australian Therapeutic Goods Administration (TGA) and Health Canada. The application reviews may be ongoing at the other regulatory agencies.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
Follow the Oncology Center of Excellence on X: @FDAOncolog.
