EPKINLY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EPKINLY (EPKINLY).
EPKINLY (epcoritamab-bysp) is a bispecific CD3xCD20 T-cell engager that binds to CD3 on T-cells and CD20 on B-cells, leading to T-cell-mediated lysis of CD20-expressing B-cells.
| Metabolism | Epcoritamab is expected to be degraded into small peptides and amino acids via general protein catabolism. |
| Excretion | Epkinly (epcoritamab) is not metabolized by CYP enzymes; elimination is primarily via catabolism into small peptides and amino acids. No dedicated excretion studies have been conducted; based on its monoclonal antibody nature, renal and biliary excretion are minimal. The expected elimination pathways are proteolytic degradation throughout the body. |
| Half-life | The terminal elimination half-life is approximately 22 days (range 14–37 days), supporting a 4-week dosing interval for subcutaneous administration. |
| Protein binding | Epcoritamab is a monoclonal antibody; protein binding is negligible as it is not bound to serum proteins in a significant manner (< 5% binding to plasma proteins). |
| Volume of Distribution | The volume of distribution is approximately 3.2–5.1 L, indicating limited extravascular distribution, consistent with a large monoclonal antibody that remains primarily in the vascular space. |
| Bioavailability | Subcutaneous: Bioavailability is approximately 80% after subcutaneous administration compared to intravenous administration. |
| Onset of Action | Subcutaneous: Initial clinical responses (e.g., reduction in target lesions) observed as early as 6 weeks (first restaging) after start of treatment. |
| Duration of Action | The duration of action depends on the treatment regimen; patients receive treatment until disease progression or unacceptable toxicity. Median duration of response in clinical trials was not reached at data cutoff, with some responses ongoing beyond 12 months. |
Administered subcutaneously at a dose of 0.6 mg/kg (maximum 40 mg) initially, then 1 mg/kg (maximum 80 mg) on Day 8, then 2 mg/kg (maximum 160 mg) on Day 15, and 3 mg/kg (maximum 240 mg) on Day 22, followed by 3 mg/kg (maximum 240 mg) every 4 weeks thereafter.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for patients with mild to moderate renal impairment (eGFR 30-89 mL/min). Not studied in severe renal impairment (eGFR <30 mL/min) or dialysis. |
| Liver impairment | No dose adjustment required for patients with mild hepatic impairment (Child-Pugh A). Not studied in moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended based on age alone; however, monitor for increased toxicity, especially in patients aged ≥65 years. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EPKINLY (EPKINLY).
| Breastfeeding | It is unknown whether epcoritamab is excreted in human milk. Maternal IgG is present in breast milk, and as a large protein, transfer is likely low. However, due to potential for adverse reactions in the breastfed infant, advise women not to breastfeed during treatment and for at least 4 months after the last dose. |
| Teratogenic Risk | Based on its mechanism of action as a bispecific CD20-directed CD3 T-cell engager, EPKINLY (epcoritamab) is expected to cause fetal B-cell lymphocytopenia and may increase risk of infection. There are no adequate human data; animal studies have not been conducted. IgG molecules cross the placenta; fetal exposure is highest in the third trimester. Potential for fetal harm cannot be excluded. |
■ FDA Black Box Warning
WARNING: CYTOKINE RELEASE SYNDROME (CRS) and IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY (ICANS). CRS can be serious or life-threatening; administer step-up dosing and monitor for symptoms. ICANS can be fatal; monitor for neurological toxicity.
| Serious Effects |
["None known"]
| Precautions | ["Cytokine release syndrome (CRS)","Immune effector cell-associated neurotoxicity syndrome (ICANS)","Infections","Cytopenias","Fetal toxicity","Tumor lysis syndrome"] |
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| Fetal Monitoring | Monitor for signs of cytokine release syndrome (CRS), neurological toxicity, and infections. Perform complete blood counts and liver function tests prior to each cycle. In pregnancy, consider fetal ultrasound to assess for growth abnormalities and B-cell depletion, though no specific monitoring guidelines exist. |
| Fertility Effects | No formal fertility studies have been conducted. Based on its mechanism of action, epcoritamab may impair fertility due to effects on B-cell populations and potential cytokine-mediated effects on reproductive tissues. The effect on human fertility is unknown. |