KIMMTRAK
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KIMMTRAK (KIMMTRAK).
KIMMTRAK (tebentafusp-tebn) is a bispecific gp100 peptide-HLA-A*02:01-directed CD3 T cell engager that binds to CD3 on T cells and gp100 peptide-HLA-A*02:01 on melanoma cells, leading to T cell activation, cytokine release, and lysis of tumor cells.
| Metabolism | Tebentafusp-tebn is expected to be catabolized into small peptides and amino acids via general protein degradation pathways; no specific metabolic pathway or enzyme has been identified. |
| Excretion | KIMMTRAK (tebentafusp) is eliminated primarily via catabolism into small peptides and amino acids; renal excretion of intact drug is negligible. No specific data on biliary/fecal elimination are available. |
| Half-life | Terminal half-life is approximately 7.1 hours (range 4.7–11.5 h) after intravenous administration, supporting weekly dosing. |
| Protein binding | Tebentafusp is approximately 95% bound to human plasma proteins, primarily to albumin. |
| Volume of Distribution | Volume of distribution at steady state (Vss) is approximately 4.4 L (range 3.6–5.4 L), suggesting limited extravascular distribution. |
| Bioavailability | KIMMTRAK is administered intravenously; bioavailability is 100% by the IV route. |
| Onset of Action | Clinical response (e.g., tumor shrinkage) is typically observed after 2–4 weeks of weekly intravenous infusions. |
| Duration of Action | Duration of action is sustained with continued weekly dosing; treatment continues until disease progression or unacceptable toxicity. |
KIMMTRAK (tebentafusp-tebn) is administered intravenously at a dose of 20 mcg on Day 1, 30 mcg on Day 8, 68 mcg on Day 15, and then 68 mcg every week thereafter.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not studied in moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established. |
| Geriatric use | No specific dose adjustment recommended for elderly patients. Clinical studies did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KIMMTRAK (KIMMTRAK).
| Breastfeeding | There are no data on the presence of tebentafusp in human milk, effects on the breastfed child, or effects on milk production. Due to the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment and for at least 1 month after the last dose. M/P ratio is unknown. |
| Teratogenic Risk | KIMMTRAK (tebentafusp-tebn) is a bispecific gp100 peptide-HLA-A*02:01-directed CD3 T cell engager. Based on its mechanism of action and animal studies, it can cause fetal harm when administered to a pregnant woman. There are no available data on use in pregnant women. In animal reproduction studies, administration of tebentafusp during organogenesis resulted in embryofetal lethality and malformations at maternal exposures below the human exposure at the recommended dose. First trimester: Risk of teratogenicity; avoid pregnancy. Second trimester: Continued risk; fetal monitoring recommended. Third trimester: Risk of adverse effects on fetal immune system; consider delaying treatment until after delivery. |
■ FDA Black Box Warning
Cytokine Release Syndrome (CRS): KIMMTRAK can cause serious or life-threatening CRS. Monitor patients during infusion and for at least 16 hours after completion of each infusion. Withhold or permanently discontinue KIMMTRAK based on severity.
| Serious Effects |
["None."]
| Precautions | ["Cytokine Release Syndrome (CRS): Monitor for signs and symptoms; manage per guidelines.","Skin reactions: Rash, pruritus, erythema; monitor and manage appropriately.","Hepatotoxicity: Elevated liver enzymes; monitor before each dose.","Hypotension: Can occur during infusion; monitor blood pressure.","Embryo-fetal toxicity: Can cause fetal harm; advise females of reproductive potential to use effective contraception."] |
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| Fetal Monitoring | Monitor fetal growth and development by serial ultrasound. Assess for signs of fetal distress or growth restriction. Baseline and periodic maternal monitoring for cytokine release syndrome (CRS), hypotension, fever, and hypoxia, as these may affect fetal wellbeing. Consider fetal echocardiogram if maternal CRS occurs due to potential placental compromise. |
| Fertility Effects | Based on animal studies, KIMMTRAK may impair fertility in females and males. In female rats, tebentafusp caused irregular estrous cycles and reduced fertility at doses below the human exposure. In male rats, effects on reproductive organs (testicular degeneration) were observed at doses below the human exposure. The potential for reversible or irreversible effects on human fertility is unknown. |