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KIMMTRAK is a brand name for Tebentafusp, supplied as a solution. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: KIMMTRAK (tebentafusp) is indicated for: the treatment of human leukocyte antigen (HLA)-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma. 1.1 Pediatrics Pediatrics (˂ 18 years of age): No data are available to Health Canada; therefore, Health Canada has not authorized an indication for…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations A positive HLA-A*02:01 genotype status is required for the selection of patients for treatment with KIMMTRAK [see WARNINGS AND PRECAUTIONS]. To minimize the risk of hypotension associated with cytokine release syndrome, administer intravenous fluids prior to starting KIMMTRAK based on clinical evaluation and the volume status of the patient [see WARNINGS AND PRECAUTIONS].
KIMMTRAK (tebentafusp) Page 5 of 29 For patients with pre-existing adrenal insufficiency on maintenance systemic corticosteroids, consider adjusting the corticosteroid dose given the risk of hypotension [see WARNINGS AND PRECAUTIONS].
2 Recommended Dose and Dosage Adjustment Recommended Dose The recommended dosage of KIMMTRAK administered intravenously is: • 20 mcg on Day 1 • 30 mcg on Day 8 • 68 mcg on Day 15 • 68 mcg once every week thereafter Treat patients until unacceptable toxicity or disease progression occur.
Administer the first three infusions of KIMMTRAK in an appropriate healthcare setting by intravenous infusion over 15-20 minutes. Monitor patients during the infusion and for at least 16 hours after the infusion is complete. If the patient does not experience Grade 2 or worse hypotension (requiring medical intervention) during or after the third infusion, administer subsequent doses in an appropriate ambulatory care setting, and monitor patients for a minimum of 30 minutes following each of these infusions [see WARNINGS AND PRECAUTIONS].
Dosage Adjustment Cytokine Release Syndrome (CRS) Identify CRS based on clinical presentation [see WARNINGS AND PRECAUTIONS]. Evaluate for and treat other causes of fever, hypoxia and hypotension. If CRS is suspected, continue monitoring until resolution and manage according to recommendations in Table 1.
Table 1:
Recommended Management and Dose Modifications for Cytokine Release Syndrome (CRS) 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 WITH Hypotension that responds to fluids and does not require vasopressors.
OR Oxygen requirement includes low flow nasal cannula (delivery of oxygen ≤ 6L/min) or blow- 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.
1 Adverse Reaction Overview The safety of KIMMTRAK was evaluated in study IMCgp100-202 (study 202), a randomized, open-label, active-controlled trial in 378 systemic therapy naive patients with metastatic uveal melanoma [see CLINICAL TRIALS].
Patients were randomized to receive either KIMMTRAK or investigator’s choice treatment (pembrolizumab, ipilimumab or dacarbazine). The most common adverse reactions (≥ 30 %) in patients treated with KIMMTRAK were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, hypo/hyperpigmentation, abdominal pain, edema, hypotension, dry skin, headache and vomiting.
Serious adverse reactions occurred in 28% of patients who received KIMMTRAK. 4%), and hypotension (2%). 4%) experienced a fatal adverse reaction (pulmonary embolism). 3% of patients who received investigator’s choice treatment. 4%). 5% of patients treated with investigator’s choice treatment (dosed every 3 weeks), with a median interruption duration of 14 and 21 days, respectively.
4%), alanine aminotransferase increase (2%), and aspartate aminotransferase increase (2%). KIMMTRAK (tebentafusp) Page 14 of 29 Adverse reactions leading to dose reduction occurred in 5% of patients who received KIMMTRAK. 4%), and rash (2%).
The most common (≥50%) laboratory abnormalities in patient who received KIMMTRAK were decreased lymphocyte count, increased creatinine, increased glucose, increased AST, increased ALT, decreased hemoglobin, and decreased phosphate.
2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. The safety of KIMMTRAK was evaluated in study IMCgp100-202 (study 202), a randomized, open-label, active-controlled trial in 378 systemic therapy naive patients with metastatic uveal melanoma [see CLINICAL TRIALS].
Immune Cytokine Release Syndrome Cytokine release syndrome (CRS), which may be life threatening, occurred in patients receiving KIMMTRAK. Manifestations of CRS may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache.
CRS (≥ Grade 2) occurred in 77% of patients in Study IMCgp100-202 who received KIMMTRAK [see ADVERSE REACTIONS]. 8% received a vasopressor for at least 1 infusion. 2% of patients. In Study IMCg100-202, 60% of patients experienced ≥ Grade 2 CRS with more than 1 infusion, with the median number of events being 2 (range 1 - 12).
The majority (84%) of episodes of CRS started the day of infusion. Among cases that resolved, the median time to resolution of CRS was 2 days. Ensure that healthcare providers administering KIMMTRAK have immediate access to medications and resuscitative equipment to manage CRS.
Ensure patients are euvolemic prior to initiating the infusions. Closely monitor patients for signs or symptoms of CRS following infusions of KIMMTRAK [see DOSAGE AND ADMINISTRATION]. Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy.
Withhold or discontinue KIMMTRAK depending on persistence and severity of CRS [see DOSAGE AND ADMINISTRATION]. Monitoring and Laboratory Tests Patients treated with KIMMTRAK must have a positive HLA-A*02:01 genotype status using a validated HLA sequencing system.
Elevations in liver enzymes occurred in patients treated with KIMMTRAK. Monitor ALT, AST, and total bilirubin. 1 Special Populations, Pregnant Women] Fertility There is no available data on effect of KIMMTRAK on fertility. 5 mL tebentafusp solution Citric acid monohydrate, disodium hydrogen phosphate, mannitol, polysorbate 20, trehalose, and water for injection KIMMTRAK (tebentafusp) Page 12 of 29 potential to use effective contraception during treatment with KIMMTRAK and for 1 week following the last dose of KIMMTRAK.
KIMMTRAK is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Increase monitoring to determine resolution or KIMMTRAK (tebentafusp) Page 6 of 29 by escalation in severity If Grade 2 CRS symptoms do not rapidly improve to Grade ≤1 within 2–3 hours, then treat as Grade 3. g. g. g. al 2019)1 Acute Skin Reactions Recommended management and dose modifications for acute skin reactions is provided in Table 2.
1 Lee W, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release Syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25:625-38.
KIMMTRAK (tebentafusp) Page 7 of 29 Table 2:
Recommended Management and Dose Modifications for Acute Skin Reactions Adverse Reactions Severity of Adverse Reaction Management Acute Skin Reactions [See WARNINGS AND PRECAUTIONS] Grade 2 or 3* (Moderate to Severe) Withhold KIMMTRAK until < Grade 1 or baseline Use local skin management and systemic antihistamine regimen and oral steroids where required.
, 2 mg/kg/day methylprednisolone or equivalent) Elevated Liver Enzymes [See WARNINGS AND PRECAUTIONS] Grade 3 or 4* 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.
, do not escalate if other Grade 3 adverse reaction occurred during initial dose escalation; resume escalation once dosage is tolerated) […]
Patients were randomized (2:1) to receive KIMMTRAK weekly by intravenous infusion according to the recommended intra-patient dosing regimen or Investigator’s choice treatment (pembrolizumab, ipilimumab, or dacarbazine) at the approved doses of these agents until disease progression or unacceptable toxicity [see DOSAGE AND ADMINISTRATION].
The median duration of exposure was 23 weeks in KIMMTRAK treated patients and 9 weeks with investigator’s choice treatment. Table 6 displays the adverse reactions observed in study IMCgp100-202 (study 202). 6 0 ALT = alanine aminotransferase; AST = aspartate aminotransferase a Investigator’s choice: i.
Dacarbazine: 1000 mg/m2 on Day 1 of each 21-day cycle ii. Ipilimumab: 3 mg/kg on Day 1 of each 21-day cycle for maximum of 4 doses iii. Pembrolizumab: 2 mg/kg up to maximum of 200 mg or 200 mg IV, where approved locally on Day 1 of each 21 -day cycle b Includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, abdominal te nderness, epigastric discomfort, flank pain, gastrointestinal pain and hepatic pain c Some of the events may be associated with CRS or may be isolated reported events d Includes fatigue and asthenia e Includes eye edema, eye swelling, eyelid edema, periorbital swelling, periorbital edema, swelling of eyelid, pharyngeal edema, lip edema, […]
Verify pregnancy status in females of reproductive potential prior to initiating KIMMTRAK treatment. Teratogenic Risk No animal reproductive and developmental toxicity studies have been conducted with KIMMTRAK to assess whether it can cause fetal harm when administered to a pregnant woman.
It is not known if KIMMTRAK has the potential to be transferred to the fetus. Advise women of the potential risk to fetus. Acute Skin Reactions Skin reactions, including rash, pruritus, erythema and cutaneous edema occurred in patients treated with KIMMTRAK.
In study IMCgp100-202, skin reactions occurred in 91% of patients treated with KIMMTRAK, including Grade 2 (44%) and Grade 3 (21%) events. Skin reactions included rash (83%), pruritus (69%), erythema (25%), and cutaneous edema (27%) [see ADVERSE REACTIONS].
The median time to onset of skin reactions was 1 day (range: 1 – 55 days). The median time to improvement to ≤ Grade 1 was approximately 6 days. Monitor patients for skin reactions. If skin reactions occur, treat with antihistamine and topical or systemic steroids based on persistence and severity of symptoms.
Withhold or permanently discontinue KIMMTRAK depending on the severity of skin reactions [see DOSAGE AND ADMINISTRATION]. Elevated Liver Enzymes In Study IMCgp100-202, increases in alanine aminotransferase or aspartate aminotransferase were observed in 65% of patients treated with KIMMTRAK.
In patients experiencing ALT/AST elevations, 73% initially occurred within the first 3 infusions with KIMMTRAK. Most patients experiencing Grade 3 or 4 ALT/AST elevations had improvement to ≤ Grade 1 within 7 days. For events that were observed outside the setting of CRS, the median time to onset was 129 days.
Grade 3 or greater elevations in liver enzymes outside the setting of CRS occurred in approximately 8% of patients. 4% of patients receiving KIMMTRAK. Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total blood bilirubin prior to the start of and during treatment with KIMMTRAK.
Withhold KIMMTRAK according to severity [see DOSAGE AND ADMINISTRATION]. 1 Pregnant Women There is no available clinical data with KIMMTRAK in pregnant woman. No animal reproductive and developmental toxicity studies have been conducted with KIMMTRAK to assess whether it can cause fetal harm when administered to a pregnant woman.
It is not known if KIMMTRAK has the potential to be transferred to the fetus. Advise women of the potential risk to fetus. 2 Breast-feeding There is no information regarding the presence of KIMMTRAK in human milk, the effect on the breastfed infant, and the effects on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for KIMMTRAK and any potential adverse effects on the breastfed infant from KIMMTRAK or from the underlying maternal condition.
It is unknown if KIMMTRAK (tebentafusp) is excreted in human milk. Precaution should be exercised because many drugs can be excreted in human milk. 3 Pediatrics No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use.
4 Geriatrics Of the 245 patients with metastatic uveal melanoma treated with KIMMTRAK on IMCgp100-202, 47% were 65 years of age and older and 9% were 75 years of age and older. No overall differences in safety or efficacy were observed between patients ≥ 65 […]