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KIMMTRAK is a brand name for Tebentafusp. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: KIMMTRAK is indicated as monotherapy for the treatment of human leukocyte antigen (HLA)-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma.
Verbatim from this product's MHRA label. Tap a section to expand.
KIMMTRAK should be administered under the supervision of a physician experienced in the use of anti-cancer immunotherapy agents. Appropriate medicinal products, including anti-IL-6 treatment and resuscitation equipment should be available.
Posology Patients treated with KIMMTRAK must have HLA-A*02:01 genotype determined by a validated HLA genotyping assay. 6). Continue treatment until disease progression or unacceptable toxicity. Atypical responses similar to immune checkpoint inhibitors have been observed.
It is recommended to continue treatment for clinically stable patients with initial evidence of disease progression until disease progression is confirmed. First three treatment doses First three doses of KIMMTRAK should be administered in a hospital setting with overnight monitoring for signs and symptoms of CRS for at least 16 hours.
Vital signs should be monitored pre-dose and at a minimum of every 4 hours until resolution of symptoms. If clinically indicated, more frequent monitoring or prolongation of hospitalisation should occur. If patients experience Grade 3 or 4 hypotension during any of the first three KIMMTRAK infusions, patients should be monitored every hour for at least 4 hours in an outpatient setting for the next three infusions.
, absence of Grade ≥ 2 hypotension requiring medical intervention), subsequent doses can be administered in appropriate out- patient ambulatory care setting. Observe patients for a minimum of 30 minutes following each infusion. Pre-medication To minimize the risk of hypotension associated with cytokine release syndrome (CRS), administer intravenous fluids prior to starting KIMMTRAK infusion based on clinical evaluation and the volume status of the patient.
For patients with pre-existing adrenal insufficiency on maintenance systemic corticosteroids, consider adjusting the corticosteroid dose to manage the risk of hypotension. Dose adjustments Evaluate for and treat other causes of fever, hypoxia and hypotension.
If CRS is suspected, identify and manage according to recommendations in Table 1. See Table 2 for management guidelines for acute skin reactions.
Table 1:
CRS Grading and Management Guidance CRS Grade* Management Grade 1 Temperature ≥ 38°C No hypotension or hypoxia Treat for symptoms as appropriate. Monitor for escalation in CRS severity Grade 2 Temperature ≥ 38°C Hypotension that responds to fluids and does not require vasopressors.
Summary of safety profile The most common adverse drug reactions (≥ 30 %) in patients treated with KIMMTRAK were cytokine release syndrome (89 %), rash (83 %), pyrexia (76 %), pruritus (69 %), fatigue (64 %), nausea (49 %), chills (48 %), hypo/hyperpigmentation (47 %), abdominal pain (45 %), oedema (45 %), hypotension (39 %), dry skin (31 %), headache (31 %) and vomiting (30 %).
4 %), and hypotension (2 %). 4 %). The frequency of treatment discontinuation due to adverse reactions was 4 % in patients who received KIMMTRAK. 4 %). No treatment-related deaths were reported. Adverse reactions resulting in dose interruption occurred in 26 % of patients who received KIMMTRAK.
4 %). 1 %). 3 % of patients who received KIMMTRAK. 1 %). Tabulated list of adverse reactions Table 3 summarizes adverse reactions that occurred in 378 metastatic uveal melanoma patients from two clinical studies (IMCgp100-102 and IMCgp100-202) that received the recommended dosing KIMMTRAK dosing regimen of 20 micrograms on Day 1, 30 micrograms on Day 8 and 68 micrograms on Day 15 and 68 micrograms weekly thereafter.
The adverse drug reaction frequency is listed by MedDRA System Organ Class (SOC) at the preferred term level. Frequencies of occurrence of adverse reactions are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000).
Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. al 2019). Adjudicated CRS is provided in lieu of investigator reported CRS. 2 Some of the events may be associated with CRS or may be isolated reported events.
3 Includes blister, dermatitis, dermatitis acneiform, dermatitis allergic, dermatitis bullous, dermatitis contact, dermatosis, drug eruption, eczema, eczema eyelids, erythema multiforme, exfoliative rash, interstitial granulomatous dermatitis, lichenification, lichenoid keratosis, palmar-plantar erythrodysaesthesia syndrome, papule, psoriasis, rash, rash erythematous, rash generalised, rash macular, rash maculo-papular, rash papular, rash pruritic, rash vesicular, seborrhoea, seborrhoeic dermatitis, skin abrasion, skin erosion, skin exfoliation, skin irritation, skin plaque, solar dermatitis, toxic skin eruption, urticaria.
Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Patient selection When considering the use of KIMMTRAK as a monotherapy for unresectable or metastatic uveal melanoma, it is important that the HLA-A*02:01 positive status of a patient is determined.
Cytokine release syndrome (CRS) CRS has occurred following KIMMTRAK infusions. Diagnosis of CRS following KIMMTRAK infusion was most frequently based on pyrexia followed by hypotension and infrequently hypoxia. Other commonly observed symptoms with CRS included chills, nausea, vomiting, fatigue, and headache.
Most patients experienced CRS following each of first three KIMMTRAK infusions, with decreasing severity and frequency. Nearly all cases of CRS started on the day of infusion. Early signs of CRS include increase in body temperature and hypotension which occur within the first 16 hours after KIMMTRAK infusion.
Monitor patients for signs or symptoms of CRS for at least 16 hours following first three infusions of tebentafusp in hospital setting with immediate access to medicinal products and resuscitative equipment to manage CRS. 2). At subsequent doses, patients should be closely monitored for at least 30 minutes after treatment for early identification of signs and symptoms of CRS.
Patients with co-morbidities, including certain cardiovascular disorders, may be at increased risk for sequalae associated with CRS. 2, Table 1). Acute skin reactions Acute skin reactions have been reported with KIMMTRAK infusion, which may be based on its mechanism of action and gp100 expression in normal melanocytes in the skin.
Acute skin reactions mainly included rash, pruritus, erythema and cutaneous oedema. Acute skin reactions typically occur following each of the first three KIMMTRAK infusions and decrease in severity and frequency with subsequent doses.
1.
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Oxygen requirement includes low flow nasal cannula (delivery of oxygen ≤ 6 L/min) or blow-by Symptom management as per Grade 1 in addition to the following measures: Administer bolus intravenous fluids as needed for hypotension Manage oxygen requirement with supplemental oxygen and additional respiratory support as needed.
g. dexamethasone 4 mg or equivalent) at least 30 minutes prior to next dose Grade 3 Temperature ≥ 38°C Require a vasopressor with or without vasopressin. g. 2 mg/kg/day methylprednisolone or equivalent) Increase monitoring to determine resolution or escalation in severity Consider administering tocilizumab.
Withhold KIMMTRAK until Grade ≤ 1. e. do not escalate) after appropriate risk versus benefit assessment and monitor patient accordingly. g. dexamethasone 4 mg or equivalent) at least 30 minutes prior to next dose Grade 4 Temperature ≥ 38°C Require multiple vasopressors.
g. CPAP, BiPAP, intubation and mechanical ventilation). al 2019). 4) Grade 2 or 3 Use local skin management and systemic antihistamine regimen. Topical corticosteroid treatment can be considered for symptomatic rash that does not respond to anti-pruritic regimen.
Consider systemic steroids for persistent or severe symptoms. 4) Grade 3 or 4a Withhold KIMMTRAK until ≤ Grade 1 or baseline. Resume KIMMTRAK at 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 mcg, or resume at same dose level if dose escalation has completed Administer intravenous corticosteroids if no improvement within 24 hours Other clinically relevant adverse reactions Grade 3a Withhold KIMMTRAK until ≤ Grade 1 […]
4 Includes fatigue and asthenia. 5 Includes achromotrichia acquired, ephelides, eyelash discolouration, eyelash hypopigmentation, hair colour changes, lentigo, pigmentation disorder, retinal depigmentation, skin depigmentation, skin discolouration, skin hyperpigmentation, skin hypopigmentation, solar lentigo, vitiligo.
6 Includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, abdominal tenderness, epigastric discomfort, flank pain, gastrointestinal pain and hepatic pain. 7 Includes eye oedema, eye swelling, eyelid oedema, periorbital swelling, periorbital oedema, swelling of eyelid, pharyngeal oedema, lip oedema, lip swelling, face oedema, generalized oedema, localised oedema, oedema, oedema peripheral, peripheral swelling, swelling, swelling face.
8 […]
No cases of Stevens-Johnson syndrome or toxic epidermal necrolysis were reported. Acute skin reactions can be managed with antihistamine and topical corticosteroids. Consider systemic steroids for persistent or severe symptoms. 2, Table 2.
Elevated liver enzymes Transient elevations in liver enzymes including aspartate transaminase/alanine aminotransferase (AST/ALT) and bilirubin have occurred following KIMMTRAK treatment. These elevations mainly occurred secondary to a CRS event and may also be attributed to underlying disease, liver metastasis, or disease progression.
Cases of liver enzyme increase can be asymptomatic. Monitor AST, ALT and total blood bilirubin prior to the start of and during treatment with KIMMTRAK. 2, Table 2). 8). Patients with pre-existing cardiovascular disorders may be at increased risk for sequalae associated with CRS and should be monitored carefully.
Any patient with signs or symptoms consistent with cardiac events should be evaluated and promptly treated. In addition, appropriate treatment should be administered for any underlying CRS as a precipitating factor. 8). Tebentafusp treatment should be administered with caution in patients with history of or predisposition to QT interval prolongation and in patients who are taking medicinal products that are known to prolong QT interval.
An electrocardiogram (ECG) should be performed in all patients before and after tebentafusp treatment during the first 3 weeks of treatment and subsequently as clinically indicated. If QTcF exceeds 500 msec or increases by ≥ 60 msec from baseline value, tebentafusp treatment should be withheld and patients should be treated for any underlying precipitating factors including electrolyte abnormalities.
Tebentafusp treatment should be resumed once QTcF interval improves to <500 msec or is < 60 msec from baseline value. 2, Table 1).