RYBREVANT FASPRO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RYBREVANT FASPRO (RYBREVANT FASPRO).
RYBREVANT FASPRO (amivantamab-vmjw) is a bispecific antibody that targets both epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET). It inhibits ligand binding and receptor activation, leading to downregulation of downstream signaling pathways (e.g., MAPK, PI3K/AKT) involved in cell proliferation and survival, and induces antibody-dependent cellular cytotoxicity (ADCC).
| Metabolism | Amivantamab-vmjw is a monoclonal antibody (human IgG1). It is catabolized into small peptides and amino acids via general protein degradation pathways (e.g., lysosomal proteolysis). No specific cytochrome P450-mediated metabolism is involved. |
| Excretion | Primarily catabolized via proteolysis; renal excretion of intact drug is minimal. Biliary/fecal excretion not characterized. |
| Half-life | Terminal elimination half-life approximately 11 days (range 7-17 days) supporting every-2-week dosing regimen. |
| Protein binding | Approximately 95-99% bound to human plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution approximately 5.4 L (not weight-adjusted), suggesting limited extravascular distribution. |
| Bioavailability | Subcutaneous: approximately 84% relative to intravenous administration. |
| Onset of Action | Subcutaneous administration: clinical response observed within 2-3 weeks after first dose. |
| Duration of Action | Duration of therapeutic effect corresponds to dosing interval of 2 weeks; sustained EGFR blockade persists for multiple half-lives after discontinuation. |
RYBREVANT (amivantamab-vmjw) is administered intravenously. The recommended dose is 1050 mg (for patients <80 kg) or 1400 mg (for patients ≥80 kg) once weekly for the first 4 weeks (Cycle 1, Days 1, 8, 15, 22), then every 2 weeks (Cycle 2 and subsequent, Days 1 and 15) starting on Day 29. Each dose is given as an IV infusion over 60 minutes (first infusion) or over 40 minutes (subsequent infusions if tolerated).
| Dosage form | VIAL |
| Renal impairment | No dose adjustment is recommended for mild to moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-89 mL/min/1.73 m²). The effect of severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease on the pharmacokinetics of amivantamab is unknown; use with caution. |
| Liver impairment | No dose adjustment is recommended for mild hepatic impairment (Child-Pugh class A). The pharmacokinetics of amivantamab have not been studied in patients with moderate or severe hepatic impairment (Child-Pugh class B or C); use with caution and monitor for toxicity. |
| Pediatric use | Safety and efficacy of RYBREVANT in pediatric patients (<18 years) have not been established; no recommended dosing. |
| Geriatric use | No specific dose adjustment is recommended for geriatric patients (≥65 years). Of the 319 patients exposed in clinical studies, 45% were aged 65 years or older; no overall differences in safety or efficacy were observed compared to younger patients. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RYBREVANT FASPRO (RYBREVANT FASPRO).
| Breastfeeding | There are no data on the presence of RYBREVANT FASPRO in human milk, effects on the breastfed infant, or effects on milk production. Maternal IgG is known to be present in human milk, but the extent of transfer and potential for infant exposure is unknown. Due to the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for at least 3 months after the last dose. M/P ratio: No data available. |
| Teratogenic Risk | Based on its mechanism of action (EGFR inhibition) and animal studies, RYBREVANT FASPRO is expected to cause fetal harm when administered to a pregnant woman. In animal reproduction studies, EGFR inhibition has been associated with embryolethality, developmental delays, and structural abnormalities. There are no adequate and well-controlled studies in pregnant women. First trimester: Highest risk for major structural anomalies due to organogenesis. Second and third trimesters: Potential for fetal growth restriction, oligohydramnios, and impaired renal function. Risk cannot be excluded throughout gestation. |
■ FDA Black Box Warning
None.
| Serious Effects |
["None listed."]
| Precautions | ["Infusion-related reactions (IRRs): May be severe. Premedicate and monitor during infusion.","Interstitial lung disease (ILD)/pneumonitis: Can be fatal. Permanently discontinue if confirmed.","Dermatologic adverse reactions: Including rash, dermatitis, and skin fissures. Manage with topical and systemic therapies.","Ocular toxicity: Including keratitis and dry eye. Monitor for visual symptoms.","Embryo-fetal toxicity: Can cause fetal harm. Advise contraception.","Venous thromboembolism (VTE): Monitor for signs and symptoms."] |
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| Fetal Monitoring | Pregnancy status should be verified prior to initiation. Women of reproductive potential should use effective contraception during treatment and for at least 3 months after the last dose. Monitor for maternal toxicity including infusion-related reactions, skin reactions, ocular toxicities, and electrolyte abnormalities. Perform serial fetal growth ultrasound if exposed during pregnancy. Assess amniotic fluid volume if oligohydramnios is suspected. |
| Fertility Effects | Based on animal studies, RYBREVANT FASPRO may impair female fertility. In female rats, administration resulted in decreased fertility and increased pre- and post-implantation loss. Effects on male fertility are unknown. Reversibility has not been assessed. |