FDA Approves Subcutaneous Amivantamab for EGFR-Positive Lung Cancer
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A Subcutaneous Revolution in EGFR-Mutated Lung Cancer: FDA Approval of Rybrevant Faspro
On December 17, 2025, the FDA approved the combination of amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) for patients with EGFR-mutated NSCLC. This subcutaneous (SC) formulation covers all indications for intravenous (IV) amivantamab, dramatically reducing the time patients spend in the clinic.
Key message: Instead of IV infusions lasting hours, the same efficacy and a lower risk of side effects can now be achieved with a subcutaneous injection taking less than 5 minutes.
1) PALOMA-3: Comparing IV and SC
The PALOMA-3 trial demonstrated that subcutaneous amivantamab had a pharmacokinetic and efficacy profile that was non-inferior (not worse) to the IV formulation. Furthermore, a statistically promising improvement in overall survival (OS) was observed in the SC arm (HR 0.62).
2) Administration and Patient Comfort
Hyaluronidase accelerates tissue absorption of the subcutaneous formulation.
• SC Duration: ~4.8 minutes.
• IV Duration: ~5 hours.
• Patient Satisfaction: 85% of patients in the SC arm described the treatment as "comfortable."
3) Efficacy: Progression-Free Survival (PFS, Months)
OS Data: Median overall survival was 12.9 months in the SC arm, whereas the target had not yet been reached in the IV arm (HR 0.62; p=0.02).
4) Differences in Safety Profiles
| Side Effect | Subcutaneous (SC) | Intravenous (IV) |
|---|---|---|
| Infusion Reactions | 13% | 66% |
| Venous Thromboembolism | 9% | 14% |
| Ease of Management | High | Low |
Clinical Practice Notes
Reduction in Infusion Reactions: The high rate of infusion reactions (66%), the biggest barrier with the IV form of Rybrevant, fell to 13% with the subcutaneous form. This may eliminate the need to split the first dose into two.
Indications: The FDA approval covers all NSCLC indications for which amivantamab (Rybrevant) is already approved.
Combination: In the trial, SC amivantamab was used together with lazertinib (Lazcluze) , an oral EGFR TKI.
DROZDOGAN Academy Commentary
The approval of Rybrevant Faspro is one of the clearest examples of "patient-centered" treatment in oncology. Reducing administration time from 5 hours to 5 minutes and improving the side effect profile without compromising efficacy will both reduce clinical workload and improve patients’ quality of life. The PALOMA-3 data herald a future in which subcutaneous ADC and antibody administration will become standard.
Source: J&J Media, December 17, 2025; PALOMA-3 Trial (NCT05388669); JCO LBA8505.
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