Tebentafusp parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Concentrate for solution for infusion formulations of tebentafusp.
Drugs List
Therapeutic Indications
Uses
Unresectable or metastatic uveal melanoma
Monotherapy in human leukocyte antigen (HLA)-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
Recommended dose of tebentafusp:
20 micrograms on Day 1
30 micrograms on Day 8
68 micrograms on Day 15
68 micrograms once a week thereafter
Additional Dosage Information
Treatment management for CRS
Grade 1 CRS (temperature greater than or equal to 38 degrees celsius, with no hypotension or hypoxia): Treat symptoms as appropriate. Monitor for escalation in severity of CRS.
Grade 2 CRS (temperature greater than or equal to 38 degrees celsius, with hypotension that responds to fluids and does not require vasopressors, and hypoxia which requires oxygen via low flow nasal cannula or blow-by): Treat symptoms as appropriate. Monitor for escalation in severity of CRS. Administer bolus IV fluids as required for hypotension. Manage oxygen requirement with supplemental oxygen and additional respiratory support as needed. Increase monitoring of patient to determine resolution or escalation in severity of CRS. If Grade 2 CRS symptoms do not rapidly improve to less than or equal to Grade 1 CRS within 2 to 3 hours, then treat as Grade 3 CRS. For recurrent or persistent Grade 2 CRS (lasting 2 to 3 hours), administer corticosteroid pre-medication (e.g. dexamethasone 4mg or equivalent) at least 30 minutes prior to the next dose.
Grade 3 CRS (temperature greater than or equal to 38 degrees celsius, requires vasopressor with or without vasopressin, and hypoxia which requires oxygen via high flow nasal cannula, face mask or non-rebreather mask or Venturi mask): Manage as per Grade 2 and include the following: Administer high-dose intravenous corticosteroid (e.g. 2mg/kg/day methylprednisolone or equivalent). Increase monitoring of patient to determine resolution or escalation in severity of CRS. Consider administering tocilizumab. Withhold tebentafusp until less than or equal to Grade 1. At next treatment, resume tebentafusp at the same dose level after appropriate risk versus benefit assessment and monitor patient accordingly. Once dose level is tolerated, can resume pre-planned dosing schedule. For Grade 3 CRS, administer corticosteroid premedication (e.g. dexamethasone 4mg or equivalent) at least 30 minutes prior to the next dose.
Grade 4 CRS (temperature greater than or equal to 38 degrees celsius, requires multiple vasopressors, and hypoxia which requires positive pressure (e.g. CPAP, BiPAP, intubation and mechanical ventilation): Permanently discontinue tebentafusp. Administer intravenous corticosteroid (e.g. 2mg/kg/day methylprednisolone or equivalent).
Dose modifications for Acute Skin Reactions and Elevated Liver Enzymes
Grade 2 or 3 acute skin reactions: Use local skin management and systemic antihistamine regimen. Topically corticosteroid treatment can be considered for symptomatic rash that does not respond to anti-pruritic regimen. Consider systemic steroids for persistent or severe symptoms. Withhold tebentafusp until resolves to less than or equal to Grade 1, then resume tebentafusp at the same dose level.
Grade 4 acute skin reactions: Permanently discontinue tebentafusp. Administer intravenous corticosteroid (e.g. 2mg/kg/day methylprednisolone or equivalent).
Grade 3 or 4 elevated liver enzymes: Withhold tebentafusp until less than or equal to Grade 1 or baseline. Resume tebentafusp at the same dose level if the elevated liver enzymes occur in the setting of Grade 3 CRS, resume escalation if next administration is tolerated. If the elevated liver enzymes occur outside the setting of Grade 3 CRS resume escalation if the current dose is less than 68 micrograms or resume at the same dose level if dose escalation has completed. Administer intravenous corticosteroid if there is no improvement within 24 hours.
Grade 3 other relevant adverse reactions: Withhold tebentafusp until less than or equal to Grade 1 or baseline. Resume tebentafusp at the same dose level.
Grade 4 other relevant adverse reactions: Permanently discontinue tebentafusp.
Cardiac Disease
QTcF exceeding 500 msec or increases by greater than or equal to 60 msec from baseline: Withhold tebentafusp treatment and treat patient for any underlying precipitating factors including electrolyte abnormalities. Once QTcF internal improves to less than 500 msec or is less than 60 msec from baseline, tebentafusp treatment can be resumed.
Administration
For intravenous infusion.
Contraindications
Children under 18 years
Breastfeeding
Pregnancy
Precautions and Warnings
Females of childbearing potential
Predisposition to prolongation of QT interval
Risk of cardiac failure
Cardiac disorder
History of cardiac disorder
History of long QT syndrome
Moderate hepatic impairment
Severe renal impairment
Confirm positive HLA-A*02:01 status prior to treatment
Maintain adequate hydration of patient prior / during treatment
Premedicate with intravenous fluids
Treatment should be initiated in hospital
Concentrate must be diluted and used as an infusion
Consult local policy on the safe use of anti-cancer drugs
Record name and batch number of administered product
Staff: Not to be handled by pregnant staff
Treatment to be administered under the supervision of a specialist
Exclude pregnancy prior to initiation of treatment
Monitor ECG
Monitor ECG before and after infusion for the first 3 weeks of treatment
Monitor for CRS during and for at least 16hrs after the first 3 infusions
Monitor hourly for 4h for next 3 infusions if grade 3 hypotension occurs
Monitor levels of hepatic enzymes and bilirubin
Monitor patients for signs and symptoms of cardiac failure
Monitor vital signs prior to treatment and every 4 hours if CRS develops
Discontinue if severe cytokine release syndrome develops
Suspend treatment if grade 3 adverse reaction occurs
Consider suspending treatment if grade 2 or 3 skin reaction occurs
Discontinue if grade 4 skin reaction occurs
Suspend treatment if grade 3 or higher elevations of hepatic transaminases
Suspend/reduce dose if QTc > 500 msec or > 60 msec increase from baseline
Permanently discontinue treatment if grade 4 adverse reactions occur
Female: Contraception required during and for 1 week after treatment
Cytokine release syndrome (CRS)
CRS has occurred following tebentafusp infusions. Monitor signs and symptoms of CRS for at least 16 hours following the first 3 tebentafusp infusions in a hospital setting with immediate access to medicinal products and resuscitative equipment to manage CRS. If CRS is observed, prompt treatment with antipyretics, intravenous fluids or corticosteroids should be initiated to avoid escalation of CRS, and monitoring should be continued until resolution.
At subsequent doses of tebentafusp, patients should be closely monitored for at least 30 minutes after infusion for early identification of signs and symptoms of CRS. Patients with co-morbidities may be at increased risk for sequelae associated with CRS.
Cardiac disease
Cardiac events have been observed in patients having received tebentafusp treatment. Patients with signs or symptoms of cardiac events should be evaluated and treated promptly. Additionally, appropriate treatment should be administered for any underlying CRS as a precipitating factor. An ECG should be performed in all patients before and after tebentafusp treatment during the first 3 weeks of treatment and then as clinically indicated.
Pregnancy and Lactation
Pregnancy
Tebentafusp is contraindicated during pregnancy.
The manufacturer states that tebentafusp is not recommended during pregnancy and in women of childbearing potential not using contraception. There are no data from the use of tebentafusp in pregnant women.
Lactation
Tebentafusp is contraindicated during breastfeeding.
The manufacturer recommends that breastfeeding should be discontinued during treatment with tebentafusp. There is insufficient information on the excretion of tebentafusp or its metabolites in human milk, therefore a risk to the newborn infant cannot be excluded.
Side Effects
Abdominal pain
Alanine aminotransferase increased
Alopecia
Anaemia
Angina pectoris
Anxiety
Arrhythmias
Arthralgia
Aspartate aminotransferase increased
Back pain
Chills
Constipation
Cough
Cytokine release syndrome
Decreased appetite
Diarrhoea
Dizziness
Dry skin
Dyspepsia
Dyspnoea
Elevated amylase levels
Elevated serum lipase
Erythema
Fatigue
Flushing
Gamma glutamyl transferase (GGT) increased
Headache
Hyperpigmentation
Hypertension
Hypocalcaemia
Hypokalaemia
Hypomagnesaemia
Hypophosphataemia
Hypopigmentation
Hypotension
Hypoxia
Increase in alkaline phosphatase
Influenza-like symptoms
Insomnia
Lymphopenia
Muscle spasm
Myalgia
Nasopharyngitis
Nausea
Night sweats
Oedema
Oropharyngeal pain
Painful extremities
Paraesthesia
Pruritus
Pyrexia
Rash
Serum bilirubin increased
Serum creatinine increased
Tachycardia
Taste disturbances
Tumour lysis syndrome
Vomiting
White blood cell count raised
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: September 2022
Reference Sources
Summary of Product Characteristics: Kimmtrak 200 micrograms/mL concentrate for solution for infusion. Immunocore Limited. Revised June 2022.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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