Kimmtrak · 4.8 Undesirable effects · 1

HOS-098909 · has-adverse-reaction-information · PDF-Seite 9

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. Adverse reactions requiring dosage interruption in ≥ 2 % of patients included fatigue (3 %; Grade 1--3), pyrexia (2.7 %; Grade 1-3), alanine aminotransferase increase (2.4 %; Grade 1-4), aspartate aminotransferase increase (2.4 %; Grade 1-3) abdominal pain (2.1 %; Grade 1-3), and lipase increased (2.1 %; Grade 1-3). Adverse reactions leading to at least one dose modification occurred in 4.2 % of patients in KIMMTRAK-treated group. Adverse reactions which required dose modification in ≥ 1 % of patients were cytokine release syndrome (1.9 %; Grade 1-3), and hypotension (1.1 %; 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. Table 3: Adverse reactions in patients treated with KIMMTRAK monotherapy Adverse reactions Infections and infestations Common Nasopharyngitis Immune system disorders Very common Cytokine release syndrome1 Metabolism and nutrition disorders Very common

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HOS-098905 · has-contraindication-information · PDF-Seite 6

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-098904 · has-indication-information · PDF-Seite 2

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.

HOS-098907 · has-interaction-information · PDF-Seite 8

No formal drug interaction studies have been performed with tebentafusp. Initiation of tebentafusp treatment causes transient release of cytokines that may suppress CYP450 enzymes. The highest drug-drug interaction risk is during the first 24 hours of the first three doses of tebentafusp in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index. These patients should be monitored for toxicity (e.g., warfarin) or drug concentrations (e.g., cyclosporine). The dose of the concomitant medicines should be adjusted as needed.

HOS-098908 · has-pregnancy-information · PDF-Seite 8

Women of childbearing potential/Contraception Women of childbearing potential should use effective contraception during treatment with tebentafusp and for at least 1 week after last dose of tebentafusp. Pregnancy There are no data from the use of tebentafusp in pregnant women. Animal reproduction studies have not been conducted with tebentafusp (see section 5.3). Tebentafusp is not recommended during pregnancy and in women of childbearing potential not using contraception. The pregnancy status in females of reproductive potential should be verified prior to initiating tebentafusp treatment. Breast-feeding There is insufficient information on the excretion of tebentafusp/metabolites in human milk. A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with tebentafusp. Fertility 8 No fertility studies have been conducted with tebentafusp (see section 5.3). The effect of tebentafusp on male and female fertility is unknown.

HOS-098906 · has-warning-information · PDF-Seite 6

Traceability 6 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. CRS rarely (1.2 %) 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. At subsequent doses, patients should be closely monitored after treatment for early identification of signs and symptoms of CRS (see section 4.2, Method of administration). Patients with co-morbidities, including cardiovascular disorders, may be at increased risk for sequalae associated with CRS. Treatment with tebentafusp has not been studied in patients with clinically significant cardiac disease (see section 5.1). Depending on persistence and severity of CRS tebentafusp treatment should be withheld or discontinued (see section 4.2, 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. Acute skin reactions mainly included rash, pruritus, erythema and cutaneous oedema (see section 4.8). Acute skin reactions typically occurred following each of the first three tebentafusp infusions and decreased in severity and frequency over time. Majority of symptoms reso

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