Amivantamab Dosing Schedule
For patients with adequate renal and hepatic function, amivantamab should be dosed based on body weight: 1,050 mg for patients <80 kg and 1,400 mg for patients ≥80 kg, administered weekly during cycle 1 (28 days), then every 2 weeks thereafter. 1
Weight-Based Dosing Strategy
The dosing regimen is stratified by body weight to optimize drug exposure and minimize pharmacokinetic variability:
This weight-based approach ensures that 87% of patients achieve exposures above the target threshold, as amivantamab exposures are 30-40% lower in patients weighing ≥80 kg compared to those <80 kg at the same dose. 1, 2
Administration Schedule
Cycle 1 (28 days)
- Weekly dosing: Administer on days 1,8,15, and 22 1
- Split first dose required: Give 350 mg on day 1, then the remainder on day 2 to mitigate infusion-related reactions 3
Cycle 2 and Beyond
- Every 2 weeks: Continue dosing every 14 days until disease progression or unacceptable toxicity 1
Pharmacokinetic Considerations
Steady-state concentrations are reached by week 13 for both the 3-week and 2-week dosing regimens, with systemic accumulation of 1.9-fold. 1 The mean terminal half-life is 14 days, supporting the every-2-week maintenance schedule. 1
Renal and Hepatic Function
No dose adjustment is required for patients with:
- Mild to moderate renal impairment (eGFR 30-89 mL/min) 1
- Mild hepatic impairment (total bilirubin ≤ULN and AST >ULN, or ULN <total bilirubin ≤1.5× ULN) 1
Important caveat: The effect of severe renal impairment (eGFR 15-29 mL/min), end-stage renal disease (eGFR <15 mL/min), or moderate to severe hepatic impairment (total bilirubin >1.5× ULN and any AST) has not been studied. 1 In these situations, close monitoring is warranted, though specific dosing recommendations are not available.
Infusion-Related Reaction Mitigation
The split first dose strategy is critical, as 90% of infusion-related reactions occur on cycle 1, day 1, with a median time-to-onset of 60 minutes. 3 Required premedications include:
- Steroid premedication before the initial dose 3
- Antihistamines and antipyretics before all doses 3
- Reduced initial infusion rates with proactive infusion interruption 3
Most infusion-related reactions (90%) are grade 1-2, and first-infusion reactions do not compromise subsequent infusions, with 85% of patients who had cycle 1, day 1 infusions aborted completing their cycle 1, day 2 infusions. 3
Subcutaneous Formulation Alternative
A subcutaneous formulation is available that demonstrates pharmacokinetic noninferiority to intravenous administration, with reduced infusion-related reactions (13% vs 66%) and median administration time of 4.8 minutes versus 5 hours for the first infusion. 4 However, the standard intravenous dosing schedule remains as outlined above for the IV formulation.