Kimmtrak

KIMMTRAK should be administered under the direction and supervision of a physician experienced in the use of anti-cancer agents and who is prepared to manage cytokine release syndrome in an environment where full resuscitation facilities are immediately available.

4). Patients treated with KIMMTRAK must have HLA-A*02:01 genotype determined by any validated HLA genotyping assay. 6). 1). Premedication To minimize the risk of hypotension associated with cytokine release syndrome (CRS), intravenous fluids should be administered prior to starting KIMMTRAK infusion based on clinical evaluation and the volume status of the patient.

3 For patients with preexisting adrenal insufficiency on maintenance systemic corticosteroids, adjusting the corticosteroid dose should be considered to manage the risk of hypotension. Dose adjustments No dose reductions of KIMMTRAK are recommended.

KIMMTRAK should be withheld or discontinued to manage adverse reactions as described in Table 1 and Table 2. If CRS is suspected, the symptoms should be identified and promptly managed 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 • Continue treatment and provide symptomatic support. Monitor for escalation in CRS severity. Grade 2 Temperature ≥ 38 °C Hypotension that responds to fluids and does not require vasopressors Oxygen requirement includes low flow nasal cannula (delivery of oxygen ≤ 6 L/min) or blow-by • Continue treatment and administer bolus intravenous fluids and oxygen by low flow nasal canula or blow-by oxygen as needed.

g. 2 mg/kg/day methylprednisolone or equivalent). g. g. 2 mg/kg/day methylprednisolone or equivalent). g. g. CPAP, BiPAP, intubation and mechanical ventilation). , 2 mg/kg/day methylprednisolone or equivalent) * Based on American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading of CRS criteria (Lee et.

al 2019). 4) Grade 2 • Withhold KIMMTRAK until Grade ≤ 1 or baseline. , non-sedating long-acting antihistamine) • Administer topical corticosteroid treatment for symptomatic rash that does not respond to anti-pruritic regimen. • For persistent symptoms, administer systemic steroids • Resume KIMMTRAK escalation if the current dose is less than 68 mcg, or resume at same dose level if dose escalation has completed Grade 3 • Withhold KIMMTRAK until Grade ≤ 1 or baseline.

Summary of safety profile The most common adverse drug reactions in patients treated with KIMMTRAK were cytokine release syndrome (88 %), rash (85 %), pyrexia (79 %), pruritus (72 %), fatigue (66 %), nausea (56 %), chills (55 %), abdominal pain (49 %), oedema (49 %), hypo/hyperpigmentation (48 %), hypotension (43 %), dry skin (35 %), headache (32 %) and vomiting (34 %).

Adverse reactions led to permanent discontinuation in 4 % of patients receiving KIMMTRAK. The most common adverse reaction that led to discontinuation of KIMMTRAK was cytokine release syndrome. Adverse reactions resulting in at least one dose interruption occurred in 26 % of KIMMTRAK-treated patients (dosed weekly) and resulted in a median of one skipped dose.

1 %; Grade 1-3). 2 % of patients in KIMMTRAK-treated group. 1 %; Grade 2-4). 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 fatigue and asthenia. 4 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.

Traceability 7 In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Cytokine release syndrome (CRS) Most patients experienced CRS following tebentafusp infusions.

Diagnosis of CRS 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. CRS has been associated with organ dysfunction, including hepatic, renal, pancreatic, cardiac, and pulmonary dysfunction.

In the majority of cases, CRS started on the day of infusion with median time to resolution of 2 days. Pyrexia was noted in nearly all cases of CRS, and in these patients, an increase in body temperature generally occurred within the first 8 hours after tebentafusp infusion.

2 %) led to treatment discontinuation. Patients should be monitored for signs or symptoms of CRS for at least 16 hours following first three infusions of tebentafusp in a hospital setting with immediate access to medicinal products and resuscitative equipment to manage CRS.

If CRS is observed, prompt treatment with supportive care including antipyretics, intravenous fluids, tocilizumab, or corticosteroids should be initiated to avoid escalation to severe or life-threatening events and monitoring should be continued until resolution.

2, Method of administration). Patients with co-morbidities, including cardiovascular disorders, may be at increased risk for sequalae associated with CRS. 1). 2, Table 1). Acute skin reactions Acute skin reactions have been reported with tebentafusp infusion, which may be based on its mechanism of action and gp100 expression in normal melanocytes in the skin.

8). Acute skin reactions typically occurred following each of the first three tebentafusp infusions and decreased in severity and frequency over time. Majority of symptoms resolved without any systemic corticosteroid or any long term sequalae.

1.