PEDIATRIC USE SECTION.

8.4 Pediatric Use. Safety and efficacy of KIMMTRAK have not been established in pediatric patients.

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following serious adverse reactions are discussed in greater detail in other sections of the label:Cytokine Release Syndrome [see Boxed Warning, Warnings and Precautions (5.1) ]Skin Reactions [see Warnings and Precautions (5.2) ]Elevated Liver Enzymes [see Warnings and Precautions (5.3) ]. Cytokine Release Syndrome [see Boxed Warning, Warnings and Precautions (5.1) ]. Skin Reactions [see Warnings and Precautions (5.2) ]. Elevated Liver Enzymes [see Warnings and Precautions (5.3) ]. The most common adverse reactions (occurring in >= 30%) are cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache and vomiting (6.1). The most common laboratory abnormalities (occurring in >=50%) are decreased lymphocyte count, increased creatinine, increased glucose, increased aspartate aminotransferase, increased alanine aminotransferase, decreased hemoglobin, and decreased phosphate (6.1).To report SUSPECTED ADVERSE REACTIONS, contact Immunocore at 1-844-IMMUNO1 (1-844-466-8661) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.. 6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.First line metastatic uveal melanomaThe safety of KIMMTRAK was evaluated in study IMCgp100-202, randomized (2:1), open-label, active-controlled trial in patients who had not received prior systemic therapy for metastatic or advanced uveal melanoma [see Clinical Studies (14)]. Patients received either KIMMTRAK administered at 20 mcg intravenously on Day 1, 30 mcg intravenously on Day 8, 68 mcg intravenously on Day 15, and 68 mcg intravenously once every week thereafter (N=245) or investigators choice treatment (N=111). The median duration of exposure was 5.3 months (range: 0.3 to 33 months) in patients treated with KIMMTRAK.Serious adverse reactions occurred in 28% of patients who received KIMMTRAK. Serious adverse reactions occurring in >= 2% of patients were cytokine release syndrome (10%), rashes (4.5%), pyrexia (2.4%), and hypotension (2%). One patient (0.4%) experienced fatal adverse reaction (pulmonary embolism).Adverse reactions led to permanent discontinuation in 3.3% of patients who received KIMMTRAK. Adverse reactions that led to permanent discontinuation of KIMMTRAK were anaphylactic reaction, brain edema, cytokine release syndrome, fatigue, hepatotoxicity, hypotension, and nausea (each 0.4%).Adverse reactions resulting in dosage interruption occurred in 25% of patients who received KIMMTRAK. Adverse reactions which required dosage interruption in >= 2% of patients included fatigue (3.7%), lipase increased (2.9%), pyrexia (2.4%), alanine aminotransferase increase (2%), and aspartate aminotransferase increase (2%).Adverse reactions leading to dose reduction occurred in 5% of patients who received KIMMTRAK. Adverse reactions which required dosage reduction in >= 2% of patients were cytokine release syndrome (2.4%), and rashes (2%).The most common adverse reactions (>=30%) in patients who received KIMMTRAK were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. 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.Table summarizes the adverse reactions observed in study IMCgp100-202.Table 4: Adverse Reactions (>=20%) in Patients with Metastatic Uveal Melanoma Who Received KIMMTRAK in Study IMCgp100-202a Represents algorithmic identification of CRS cases based on ASTCT grading criteria (Lee et al. 2019). Represents composite of multiple related terms.Adverse ReactionsKIMMTRAK(N=245)Investigators Choice (pembrolizumab, or ipilimumab, or dacarbazine)(N=111)All Grades(%)Grade or 4(%)All Grades(%)Grade or 4(%)Immune system disordersCytokine release syndromea 890.82.70Skin and subcutaneous tissue disordersRashb 8318280Pruritus694.5230Dry skin3103.60Skin Hypopigmentationb 28NA5NAErythema2400.90Hair color changesb 20NA0NAGeneral disorders and administration site conditionsPyrexia763.770.9Fatigueb 646420.9Chills480.43.60Edemab 450100Gastrointestinal disordersNausea492260.9Abdominal painb 452.9333.6Vomiting301.290Diarrhea251.2202.7Vascular disordersHypotension393.32.70Nervous system disordersHeadache310.4100.9Musculoskeletal and connective tissue disordersArthralgia220.8160Clinically relevant adverse reactions occurring in 20% of patients who received KIMMTRAK included back pain, decreased appetite, constipation, hypertension, tachycardia or sinus tachycardia, dyspnea, paresthesia, dizziness, flushing, muscle spasms, myalgia, pain in extremity, alopecia, skin hyperpigmentation, influenza-like illness, oropharyngeal pain and night sweats.Table summarizes the selected laboratory abnormalities observed in study IMCgp100-202.Table 5: Selected Laboratory Abnormalities (>= 10%) worsening from baseline in patients who received KIMMTRAK versus Investigators ChoiceAlk Phos Alkaline Phosphatase; AST=aspartate aminotransferase; ALT=alanine aminotransferase The denominator used to calculate the rate varied from 242 to 245 for KIMMTRAK and 105 to 109 for IC based on the number of patients with baseline value and at least one post-treatment value for the laboratory assessment.KIMMTRAKa(N=245)Investigators Choicea(pembrolizumab, or ipilimumab, or dacarbazine)(N=111)Grades 1-4 (%)Grades 3-4 (%)Grades 1-4 (%)Grades 3-4 (%)HEMATOLOGYLymphocyte count decreased 9156261.8Hemoglobin decreased 510.8200.9Platelet count decreased 160150.9Neutrophil count decreased 14281.8CHEMISTRYCreatinine increased 870.4730Glucose increased 663.3394.6AST increased 5513391.9ALT increased 529291.8Phosphate decreased 5111202Albumin decreased 472.1140.9Calcium decreased 451.6151.9Lipase increased 3715286Magnesium decreased 34080Alk phos increased 342.9361.8Sodium decreased 302.9150.9Potassium increased 291.6150.9Bilirubin increased 274.1147Amylase increased 234.1181Glucose decreased 180.44.60Potassium decreased 170.880.9Calcium increased 1303.70. 6.2 Immunogenicity. As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.Treatment-emergent anti-drug antibodies (ADA) against tebentafusp-tebn were detected in 33% and 29% of patients receiving tebentafusp-tebn across all doses in study IMCgp100-102 and study IMCgp100-202, respectively. The median onset time to ADA formation was 6-9 weeks after tebentafusp-tebn treatment. The ability of these binding ADAs to neutralize tebentafusp-tebn is unknown. The tebentafusp-tebn clearance increased in patients with high titer ADAs [see Clinical Pharmacology (12.3)]. Exploratory analyses with limited data suggest that formation of ADA does not appear to have clinically significant effect on frequency or severity of hypersensitivity related adverse reactions and no observed sign of decreased overall survival.

BOXED WARNING SECTION.

WARNING: CYTOKINE RELEASE SYNDROME. Cytokine Release Syndrome (CRS), which may be serious or life-threatening, occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours following first three infusions and then as clinically indicated [(see Dosage and Administration (2.2), see Warnings and Precautions (5.1)].. WARNING: CYTOKINE RELEASE SYNDROMECytokine Release Syndrome (CRS), which may be serious or life-threatening, occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours following first three infusions and then as clinically indicated (2.2, 5.1).

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. No carcinogenicity or genotoxicity studies have been conducted with tebentafusp-tebn.No studies have been conducted to evaluate the effects of tebentafusp-tebn on fertility.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Tebentafusp-tebn is bispecific gp100 peptide-HLA-A02:01 directed cell receptor CD3 cell engager. The TCR arm binds to gp100 peptide presented by human leukocyte antigen-A02:01 (HLA-A02:01) on the cell surface of uveal melanoma tumor cells.In vitro, tebentafusp-tebn bound to HLA-A02:01-positive uveal melanoma cells and activated polyclonal cells to release inflammatory cytokines and cytolytic proteins, which results in direct lysis of uveal melanoma tumor cells.. 12.2 Pharmacodynamics. Lymphocyte counts declined the day after the first doses and returned to baseline prior to subsequent doses.Serum levels of cytokines (IFN-, TNF, IL-2, IL-6, IL-10 and IL-1RA) and chemokines (CXCL9, CXCL10, CXCL11, hepatocyte growth factor, and monocyte chemoattractant protein-1) were increased during the first three doses of KIMMTRAK with peak levels between to 24 hours after treatment with KIMMTRAK and levels returned to baseline prior to subsequent doses. In subsequent treatment cycles, cytokine elevation occurred in fewer patients with lesser intensity compared to the first doses.The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of KIMMTRAK have not been fully characterized.. 12.3 Pharmacokinetics. After single dose administration, tebentafusp-tebn Cmax and AUC0-7d increased in an approximately dose proportional manner from 20 to 68 mcg (0.3 to times the approved recommended dose). Following administration of the approved recommended dosage in patients with metastatic uveal melanoma, the steady-state geometric mean (% CV) Cmax of tebentafusp-tebn is 13 ng/mL (34.6%) and AUC0-7d is 4.6 ng.day/mL (23%) with no accumulation.DistributionTebentafusp-tebn geometric mean (% CV) steady-state volume of distribution is 7.56 (24%).EliminationThe geometric mean clearance of tebentafusp-tebn is 16.4 L/d (CV: 24.5%) and median terminal half-life is 7.5 hours (range: 6.8-7.5 hours).MetabolismTebentafusp-tebn is expected to be catabolized into small peptides and amino acids.Specific PopulationsNo clinically significant difference in the pharmacokinetics of tebentafusp-tebn were identified based on weight (43 to 163 kg), sex (48% female), age (23 to 91 years), or mild to moderate renal impairment based on creatinine clearance (CLcr) estimated by C-G formula (CLcr 30 to 89 mL/min) or mild hepatic impairment as measured by total bilirubin (TB) and aspartate aminotransferase (AST) (TB <= upper limit of normal (ULN) and AST ULN or TB 1 to 1.5x ULN and any AST).Tebentafusp-tebn has not been studied in patients with severe (CLcr 30 mL/min) renal impairment or in patients with moderate (TB >1.5 to 3x ULN, any AST) to severe (TB 3 to 10x ULN, any AST) hepatic impairment.ImmunogenicityMedian titer in the ADA-positive subgroup was 8192 across the 67 treatment cycles. The exposure (AUC0-7 days) of tebentafusp-tebn decreased by 97% and terminal half-life decreased to 10-14 minutes in patients with ADA titers greater than 8192.Drug InteractionElevation of certain proinflammatory cytokines may suppress CYP450 enzyme activities.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. Study IMCgp100-202: First line metastatic uveal melanomaKIMMTRAK was evaluated in IMCgp100-202, randomized, open-label, multicenter trial (NCT03070392) that enrolled patients with metastatic uveal melanoma (N=378). Patients were required to be HLA-A02:01 genotype positive identified by central assay. Patients were excluded if they received prior systemic therapy for metastatic or advanced uveal melanoma or localized liver-directed therapy. Prior surgical resection of oligometastatic disease was permitted. Patients with clinically significant cardiac disease or the presence of symptomatic or untreated brain metastasis were excluded.Patients were randomized (2:1) to receive KIMMTRAK weekly by intravenous infusion administered at 20 mcg intravenously on Day 1, 30 mcg intravenously on Day 8, 68 mcg intravenously on Day 15, and 68 mcg intravenously once every week thereafter (N=252) or Investigators choice (N=126) of pembrolizumab, ipilimumab, or dacarbazine. Randomization was stratified by lactate dehydrogenase (LDH) level at study entry. Across both arms, patients stopped treatment for disease progression, unless the patient was otherwise deriving benefit, or for unacceptable toxicity.The major efficacy outcome was overall survival (OS). Additional efficacy outcomes were investigator-assessed progression free survival (PFS) and objective response rate (ORR) per RECIST 1.1.The median age was 64 years (range 23 to 92 years); 50% were female; 87% were White, and 12% were unreported or unknown race. The reported ethnicity was Hispanic or Latino in 2.4% of patients. Baseline ECOG performance status was (73%), (21%), or (0.3%); 36% had elevated LDH level; and 94% had liver metastasis.The efficacy results are summarized in Table and Figure 1.Table 6: Efficacy Results in Study IMCgp100-202CI= Confidence Interval, HR= Hazard Ratio Based on prespecified interim analysis Hazard ratio is from cox proportional hazards model stratified by LDH status Two-sided p-value based on log rank test stratified by LDH Compared to the interim efficacy boundary of 0.006 Final PFS analysis Compared to the efficacy boundary of 0.05. Not formally testedKIMMTRAK(N=252)Investigators Choice (pembrolizumab, or ipilimumab, or dacarbazine)(N=126)Overall Survival (OS)1Number of deaths87 (34.5%)63 (50%)Median in months (95% CI)21.7 (18.6, 28.6)16 (9.7, 18.4)HR (95% CI)2 0.51 (0.37, 0.71)p-value3, <0.0001Progression-free Survival5Number (%) of patients with event198 (78.6%)97 (77%)Median in months (95% CI)3.3 (3, 5)2.9 (2.8, 3)HR (95% CI)2 0.73 (0.58, 0.94)p-value3, 0.0139Objective Response Rate (95% CI)79.1% (5.9, 13.4)4.8% (1.8, 10.1)Complete Response1 (0.4%)0Partial Response22 (8.7%)6 (4.8%)Figure 1: Kaplan-Meier Curves of Overall Survival in Study IMCgp100-202 Figure 1.

CLINICAL TRIALS EXPERIENCE SECTION.

6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.First line metastatic uveal melanomaThe safety of KIMMTRAK was evaluated in study IMCgp100-202, randomized (2:1), open-label, active-controlled trial in patients who had not received prior systemic therapy for metastatic or advanced uveal melanoma [see Clinical Studies (14)]. Patients received either KIMMTRAK administered at 20 mcg intravenously on Day 1, 30 mcg intravenously on Day 8, 68 mcg intravenously on Day 15, and 68 mcg intravenously once every week thereafter (N=245) or investigators choice treatment (N=111). The median duration of exposure was 5.3 months (range: 0.3 to 33 months) in patients treated with KIMMTRAK.Serious adverse reactions occurred in 28% of patients who received KIMMTRAK. Serious adverse reactions occurring in >= 2% of patients were cytokine release syndrome (10%), rashes (4.5%), pyrexia (2.4%), and hypotension (2%). One patient (0.4%) experienced fatal adverse reaction (pulmonary embolism).Adverse reactions led to permanent discontinuation in 3.3% of patients who received KIMMTRAK. Adverse reactions that led to permanent discontinuation of KIMMTRAK were anaphylactic reaction, brain edema, cytokine release syndrome, fatigue, hepatotoxicity, hypotension, and nausea (each 0.4%).Adverse reactions resulting in dosage interruption occurred in 25% of patients who received KIMMTRAK. Adverse reactions which required dosage interruption in >= 2% of patients included fatigue (3.7%), lipase increased (2.9%), pyrexia (2.4%), alanine aminotransferase increase (2%), and aspartate aminotransferase increase (2%).Adverse reactions leading to dose reduction occurred in 5% of patients who received KIMMTRAK. Adverse reactions which required dosage reduction in >= 2% of patients were cytokine release syndrome (2.4%), and rashes (2%).The most common adverse reactions (>=30%) in patients who received KIMMTRAK were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. 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.Table summarizes the adverse reactions observed in study IMCgp100-202.Table 4: Adverse Reactions (>=20%) in Patients with Metastatic Uveal Melanoma Who Received KIMMTRAK in Study IMCgp100-202a Represents algorithmic identification of CRS cases based on ASTCT grading criteria (Lee et al. 2019). Represents composite of multiple related terms.Adverse ReactionsKIMMTRAK(N=245)Investigators Choice (pembrolizumab, or ipilimumab, or dacarbazine)(N=111)All Grades(%)Grade or 4(%)All Grades(%)Grade or 4(%)Immune system disordersCytokine release syndromea 890.82.70Skin and subcutaneous tissue disordersRashb 8318280Pruritus694.5230Dry skin3103.60Skin Hypopigmentationb 28NA5NAErythema2400.90Hair color changesb 20NA0NAGeneral disorders and administration site conditionsPyrexia763.770.9Fatigueb 646420.9Chills480.43.60Edemab 450100Gastrointestinal disordersNausea492260.9Abdominal painb 452.9333.6Vomiting301.290Diarrhea251.2202.7Vascular disordersHypotension393.32.70Nervous system disordersHeadache310.4100.9Musculoskeletal and connective tissue disordersArthralgia220.8160Clinically relevant adverse reactions occurring in 20% of patients who received KIMMTRAK included back pain, decreased appetite, constipation, hypertension, tachycardia or sinus tachycardia, dyspnea, paresthesia, dizziness, flushing, muscle spasms, myalgia, pain in extremity, alopecia, skin hyperpigmentation, influenza-like illness, oropharyngeal pain and night sweats.Table summarizes the selected laboratory abnormalities observed in study IMCgp100-202.Table 5: Selected Laboratory Abnormalities (>= 10%) worsening from baseline in patients who received KIMMTRAK versus Investigators ChoiceAlk Phos Alkaline Phosphatase; AST=aspartate aminotransferase; ALT=alanine aminotransferase The denominator used to calculate the rate varied from 242 to 245 for KIMMTRAK and 105 to 109 for IC based on the number of patients with baseline value and at least one post-treatment value for the laboratory assessment.KIMMTRAKa(N=245)Investigators Choicea(pembrolizumab, or ipilimumab, or dacarbazine)(N=111)Grades 1-4 (%)Grades 3-4 (%)Grades 1-4 (%)Grades 3-4 (%)HEMATOLOGYLymphocyte count decreased 9156261.8Hemoglobin decreased 510.8200.9Platelet count decreased 160150.9Neutrophil count decreased 14281.8CHEMISTRYCreatinine increased 870.4730Glucose increased 663.3394.6AST increased 5513391.9ALT increased 529291.8Phosphate decreased 5111202Albumin decreased 472.1140.9Calcium decreased 451.6151.9Lipase increased 3715286Magnesium decreased 34080Alk phos increased 342.9361.8Sodium decreased 302.9150.9Potassium increased 291.6150.9Bilirubin increased 274.1147Amylase increased 234.1181Glucose decreased 180.44.60Potassium decreased 170.880.9Calcium increased 1303.70.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. None.. None (4).

DESCRIPTION SECTION.

11 DESCRIPTION. Tebentafusp-tebn is bispecific gp100 peptide-HLA-directed cell receptor CD3 cell engager. Tebentafusp-tebn has an approximate molecular weight of 77 kDa. Tebentafusp-tebn is produced by recombinant DNA technology in Escherichia coli cells.KIMMTRAK (tebentafusp-tebn) injection is supplied in single-dose vial as sterile, preservative-free, clear, colorless or slightly yellowish solution for intravenous administration by infusion.Each single-dose vial contains tebentafusp-tebn (100 mcg), citric acid monohydrate (0.95 mg), di-sodium hydrogen phosphate (2.91 mg), mannitol (5 mg), polysorbate 20 (0.1 mg) trehalose (25 mg), and water for injection, with pH of 6.5.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Recommended dosage: 20 mcg intravenously on Day 1, 30 mcg intravenously on Day 8, 68 mcg intravenously on Day 15, and 68 mcg intravenously once every week thereafter (2.2).Dilute and administer by intravenous infusion over 15-20 minutes (2.2, 2.4).See Full Prescribing Information for instructions on preparation and administration of the diluted solution for intravenous infusion (2.2, 2.4).Dosage interruption or permanent discontinuation may be required based on individual safety and tolerability (2.3).. Recommended dosage: 20 mcg intravenously on Day 1, 30 mcg intravenously on Day 8, 68 mcg intravenously on Day 15, and 68 mcg intravenously once every week thereafter (2.2).. Dilute and administer by intravenous infusion over 15-20 minutes (2.2, 2.4).. See Full Prescribing Information for instructions on preparation and administration of the diluted solution for intravenous infusion (2.2, 2.4).. Dosage interruption or permanent discontinuation may be required based on individual safety and tolerability (2.3).. 2.1 Patient Selection. Select patients for treatment of unresectable or metastatic uveal melanoma with KIMMTRAK based on positive HLA-A02:01 genotyping test [see Clinical Studies (14)]. An FDA-approved test for the detection of HLA-A02:01 genotyping is not currently available.. 2.2 Recommended Dosage. The recommended dosage of KIMMTRAK administered intravenously is:20 mcg on Day 130 mcg on Day 868 mcg on Day 1568 mcg once every week thereafterTreat 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 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 minimum of 30 minutes following each of these infusions [see Warnings and Precautions (5.1)].. 20 mcg on Day 1. 30 mcg on Day 8. 68 mcg on Day 15. 68 mcg once every week thereafter. 2.3 Dosage Modifications for Adverse Reactions. No dosage reduction for KIMMTRAK is recommended. Dosage modifications for KIMMTRAK for adverse reactions are summarized in Table 1.Table 1: Dose Modifications for Adverse Reactionsa Based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (NCI CTCAEv4.03).Adverse ReactionSeverityKIMMTRAK Dosage ModificationsCytokine Release Syndrome (CRS)[see Warnings and Precautions (5.1)]Moderate defined as temperature >= 38C withHypotension that responds to fluids (does not require vasopressors) orHypoxia requiring low flow nasal canula (<= L/min) or blow-by oxygen If hypotension and hypoxia do not improve within hours or CRS worsens, escalate care and manage according to next higher level of severityFor moderate CRS that is persistent (lasting 2-3 hours) or recurrent, administer corticosteroid premedication (e.g. dexamethasone mg or equivalent) at least 30 minutes prior to next doseSevere defined as temperature >= 38C with Hemodynamic instability requiring vasopressor (with or without vasopressin) orWorsening hypoxia or respiratory distress requiring high flow nasal canula (> L/min oxygen) or face mask Withhold KIMMTRAK until CRS and sequelae have resolved Administer intravenous corticosteroid (e.g., mg/kg/day methylprednisolone or equivalent)Resume KIMMTRAK at same dose level (i.e., do not escalate if severe CRS occurred during initial dose escalation; resume escalation once dosage is tolerated)For severe CRS, administer corticosteroid premedication (e.g. dexamethasone mg or equivalent) at least 30 minutes prior to next doseLife threatening defined as temperature >= 38C with Hemodynamic instability requiring multiple vasopressors (excluding vasopressin)Worsening hypoxia or respiratory distress despite oxygen administration requiring positive pressure Permanently discontinue KIMMTRAKAdminister intravenous corticosteroid (e.g., mg/kg/day methylprednisolone or equivalent)Skin Reactions[see Warnings and Precautions (5.2)]Grade or 3a Withhold KIMMTRAK until <= Grade or baselineResume KIMMTRAK at same dose level (i.e., do not escalate if Grade skin reactions occurred during initial dose escalation; resume escalation once dosage is tolerated)For persistent reactions not responding to oral steroids, consider intravenous corticosteroid (e.g., mg/kg/day methylprednisolone or equivalent)Grade 4a Permanently discontinue KIMMTRAKAdminister intravenous corticosteroid (e.g., mg/kg/day methylprednisolone or equivalent)Elevated Liver Enzymes[see Warnings and Precautions (5.3)]Grade or 4a Withhold KIMMTRAK until <= Grade or baseline.Resume KIMMTRAK at same dose level if the elevated liver enzymes occur in the setting of Grade CRS; resume escalation if next administration is tolerated.If the elevated liver enzymes occur outside the setting of Grade CRSresume 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 hoursOther Adverse Reactions[see Adverse Reactions (6.1)]Grade 3a Withhold KIMMTRAK until <= Grade or baselineResume KIMMTRAK at same dose level (i.e., do not escalate if other Grade adverse reaction occurred during initial dose escalation; resume escalation once dosage is tolerated)Grade 4a Permanently discontinue KIMMTRAK. Hypotension that responds to fluids (does not require vasopressors) or. Hypoxia requiring low flow nasal canula (<= L/min) or blow-by oxygen. If hypotension and hypoxia do not improve within hours or CRS worsens, escalate care and manage according to next higher level of severity. For moderate CRS that is persistent (lasting 2-3 hours) or recurrent, administer corticosteroid premedication (e.g. dexamethasone mg or equivalent) at least 30 minutes prior to next dose. Hemodynamic instability requiring vasopressor (with or without vasopressin) or. Worsening hypoxia or respiratory distress requiring high flow nasal canula (> L/min oxygen) or face mask. Withhold KIMMTRAK until CRS and sequelae have resolved Administer intravenous corticosteroid (e.g., mg/kg/day methylprednisolone or equivalent). Resume KIMMTRAK at same dose level (i.e., do not escalate if severe CRS occurred during initial dose escalation; resume escalation once dosage is tolerated). For severe CRS, administer corticosteroid premedication (e.g. dexamethasone mg or equivalent) at least 30 minutes prior to next dose. Hemodynamic instability requiring multiple vasopressors (excluding vasopressin). Worsening hypoxia or respiratory distress despite oxygen administration requiring positive pressure. Permanently discontinue KIMMTRAK. Administer intravenous corticosteroid (e.g., mg/kg/day methylprednisolone or equivalent). Withhold KIMMTRAK until <= Grade or baseline. Resume KIMMTRAK at same dose level (i.e., do not escalate if Grade skin reactions occurred during initial dose escalation; resume escalation once dosage is tolerated). For persistent reactions not responding to oral steroids, consider intravenous corticosteroid (e.g., mg/kg/day methylprednisolone or equivalent). Permanently discontinue KIMMTRAK. Administer intravenous corticosteroid (e.g., mg/kg/day methylprednisolone or equivalent). Withhold KIMMTRAK until <= Grade or baseline.. Resume KIMMTRAK at same dose level if the elevated liver enzymes occur in the setting of Grade CRS; resume escalation if next administration is tolerated.. If the elevated liver enzymes occur outside the setting of Grade CRSresume escalation if the current dose is less than 68 mcg, or resume at same dose level if dose escalation has completed 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. Withhold KIMMTRAK until <= Grade or baseline. Resume KIMMTRAK at same dose level (i.e., do not escalate if other Grade adverse reaction occurred during initial dose escalation; resume escalation once dosage is tolerated). Permanently discontinue KIMMTRAK. 2.4 Preparation and Administration. PreparationA 2-step dilution process is required for preparation of the final KIMMTRAK dose for infusion.Use aseptic technique for dilution and preparation of intravenous infusion solutions.Visually inspect parenteral drug products and infusion bags for particulate matter and discoloration prior to administration, whenever solution and container permit.Step 1: Preparation of the Infusion BagTo prevent adsorption of tebentafusp-tebn to the infusion bag and other components of the drug delivery system, prepare an Albumin (Human) in 0.9% Sodium Chloride Injection, USP solution as follows:Using 1 mL syringe with graduations of decimal places and sterile needle, withdraw the calculated volume of Albumin (Human) into the syringe (see Table below) and add to the 100 mL 0.9% Sodium Chloride Injection, USP bag constructed of polyolefins (PO) [such as polyethylene (PE) and polypropylene (PP)] or polyvinyl chloride (PVC) to make final Albumin (Human) concentration of 250 mcg/mL.Table 2: Examples of Albumin (Human) Concentration and Volumes Albumin (Human); use concentration as per local availability. Examples include but are not restricted to the following strengths: 5%, 20%, or 25%.Albumin (Human) concentrationAlbumin (Human) volume for addition to 100 mL 0.9% Sodium Chloride Injection, USP Infusion Bag to prepare concentration of 250 mcg/mL Albumin (Human) in 0.9% Sodium Chloride Injection, USP 5% (50 g/L)0.5 mL 20% (200 g/L)0.13 mL 25% (250 g/L)0.1 mL Gently homogenize the prepared solution by completing the following steps:Invert the infusion bag so that the bag is upside down with the entry port positioned on top. Then tap the side of the port tubing to ensure that any residual solution is released into the bulk solution.Mix the prepared solution by gently rotating the bag lengthwise 360 degrees from the inverted position at least times. Do not shake the infusion bag. Repeat (i) and (ii) an additional three times. Step 2- Preparation of KIMMTRAK Solution for InfusionDo not shake the KIMMTRAK vial.Using 1 mL syringe with graduations of decimal places and sterile needle, withdraw the required volume of KIMMTRAK 100 mcg/ 0.5 mL as per the dose required (shown in Table below) and add to the prepared 100 mL infusion bag containing 0.9% Sodium Chloride Injection, USP plus Albumin (Human).Discard the single-dose vial containing the unused portion of KIMMTRAK in accordance with local requirements. Do not prepare more than one dose from the vial.Table 3: KIMMTRAK Volumes Required for Addition to the Infusion Bag Day of treatmentDose (mcg) of KIMMTRAKVolume (mL) of KIMMTRAKDay 1200.1Day 8300.15Day 15 and weekly thereafter680.34 Mix the infusion bag by following the same procedure outlined in Step 1b. AdministrationImmediately administer the diluted solution via intravenous infusion over 15-20 minutes through dedicated intravenous line. sterile, non-pyrogenic, low protein binding 0.2 micron in-line filter infusion set should be used. Administer the entire contents of the KIMMTRAK infusion bag.Administer the prepared infusion bag within hours from the time of preparation including the duration of infusion. During the 4-hour window, the KIMMTRAK infusion bag should remain at room temperature.If not used immediately, store the KIMMTRAK infusion bag in refrigerator at 2C to 8C (36F to 46F) and infuse within 24 hours from the time of preparation, which includes the storage time in the refrigerator, the time allowed for equilibration of the infusion bag to room temperature, and the duration of the infusion.Once removed from the refrigerator, do not refrigerate KIMMTRAK infusion bag again. Do not freeze. Discard unused KIMMTRAK solution beyond the recommended storage time.Do not mix KIMMTRAK with other drugs or administer other drugs through the same intravenous line. Upon completion of KIMMTRAK infusion, flush the infusion line with adequate volume of sterile 0.9% Sodium Chloride Injection, USP to ensure that the entire contents of the infusion bag are administered.. 2-step dilution process is required for preparation of the final KIMMTRAK dose for infusion.. Use aseptic technique for dilution and preparation of intravenous infusion solutions.. Visually inspect parenteral drug products and infusion bags for particulate matter and discoloration prior to administration, whenever solution and container permit.. Using 1 mL syringe with graduations of decimal places and sterile needle, withdraw the calculated volume of Albumin (Human) into the syringe (see Table below) and add to the 100 mL 0.9% Sodium Chloride Injection, USP bag constructed of polyolefins (PO) [such as polyethylene (PE) and polypropylene (PP)] or polyvinyl chloride (PVC) to make final Albumin (Human) concentration of 250 mcg/mL.Table 2: Examples of Albumin (Human) Concentration and Volumes Albumin (Human); use concentration as per local availability. Examples include but are not restricted to the following strengths: 5%, 20%, or 25%.Albumin (Human) concentrationAlbumin (Human) volume for addition to 100 mL 0.9% Sodium Chloride Injection, USP Infusion Bag to prepare concentration of 250 mcg/mL Albumin (Human) in 0.9% Sodium Chloride Injection, USP 5% (50 g/L)0.5 mL 20% (200 g/L)0.13 mL 25% (250 g/L)0.1 mL Gently homogenize the prepared solution by completing the following steps:Invert the infusion bag so that the bag is upside down with the entry port positioned on top. Then tap the side of the port tubing to ensure that any residual solution is released into the bulk solution.Mix the prepared solution by gently rotating the bag lengthwise 360 degrees from the inverted position at least times. Do not shake the infusion bag. Repeat (i) and (ii) an additional three times. Invert the infusion bag so that the bag is upside down with the entry port positioned on top. Then tap the side of the port tubing to ensure that any residual solution is released into the bulk solution.. Mix the prepared solution by gently rotating the bag lengthwise 360 degrees from the inverted position at least times. Do not shake the infusion bag. Repeat (i) and (ii) an additional three times.. Do not shake the KIMMTRAK vial.. Using 1 mL syringe with graduations of decimal places and sterile needle, withdraw the required volume of KIMMTRAK 100 mcg/ 0.5 mL as per the dose required (shown in Table below) and add to the prepared 100 mL infusion bag containing 0.9% Sodium Chloride Injection, USP plus Albumin (Human).. Discard the single-dose vial containing the unused portion of KIMMTRAK in accordance with local requirements. Do not prepare more than one dose from the vial.Table 3: KIMMTRAK Volumes Required for Addition to the Infusion Bag Day of treatmentDose (mcg) of KIMMTRAKVolume (mL) of KIMMTRAKDay 1200.1Day 8300.15Day 15 and weekly thereafter680.34 Mix the infusion bag by following the same procedure outlined in Step 1b. Immediately administer the diluted solution via intravenous infusion over 15-20 minutes through dedicated intravenous line. sterile, non-pyrogenic, low protein binding 0.2 micron in-line filter infusion set should be used. Administer the entire contents of the KIMMTRAK infusion bag.. Administer the prepared infusion bag within hours from the time of preparation including the duration of infusion. During the 4-hour window, the KIMMTRAK infusion bag should remain at room temperature.. If not used immediately, store the KIMMTRAK infusion bag in refrigerator at 2C to 8C (36F to 46F) and infuse within 24 hours from the time of preparation, which includes the storage time in the refrigerator, the time allowed for equilibration of the infusion bag to room temperature, and the duration of the infusion.. Once removed from the refrigerator, do not refrigerate KIMMTRAK infusion bag again. Do not freeze. Discard unused KIMMTRAK solution beyond the recommended storage time.. Do not mix KIMMTRAK with other drugs or administer other drugs through the same intravenous line. Upon completion of KIMMTRAK infusion, flush the infusion line with adequate volume of sterile 0.9% Sodium Chloride Injection, USP to ensure that the entire contents of the infusion bag are administered.

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. Injection: 100 mcg/0.5 mL clear, colorless to slightly yellowish solution in single-dose vial. Injection: 100 mcg/0.5 mL solution in single-dose vial (3).

FEMALES & MALES OF REPRODUCTIVE POTENTIAL SECTION.

8.3 Females and Males of Reproductive Potential. KIMMTRAK may cause fetal harm when administered to pregnant woman [see Use in Specific Populations (8.1)].Pregnancy TestingVerify pregnancy status in females of reproductive potential prior to initiating KIMMTRAK treatment.ContraceptionFemales Advise female of reproductive potential to use effective contraception during treatment and for week following the last dose of KIMMTRAK [see Use in Specific Populations (8.1)].

GERIATRIC USE SECTION.

8.5 Geriatric Use. 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 years of age compared to younger adult patients.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. How SuppliedEach KIMMTRAK (tebentafusp-tebn) injection carton (NDC 80446-401-01) contains:One single-dose vial containing 100 mcg of tebentafusp-tebn in 0.5 mL of sterile, preservative-free, clear, colorless or slightly yellowish solution.The vial stopper is not made with natural rubber latex.Storage and HandlingStore KIMMTRAK vials in the original carton refrigerated at 2C to 8C (36F to 46F) and protect from light until time of use. Do not freeze. Do not shake.. One single-dose vial containing 100 mcg of tebentafusp-tebn in 0.5 mL of sterile, preservative-free, clear, colorless or slightly yellowish solution.. Store KIMMTRAK vials in the original carton refrigerated at 2C to 8C (36F to 46F) and protect from light until time of use. Do not freeze. Do not shake.

IMMUNOGENICITY.

6.2 Immunogenicity. As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.Treatment-emergent anti-drug antibodies (ADA) against tebentafusp-tebn were detected in 33% and 29% of patients receiving tebentafusp-tebn across all doses in study IMCgp100-102 and study IMCgp100-202, respectively. The median onset time to ADA formation was 6-9 weeks after tebentafusp-tebn treatment. The ability of these binding ADAs to neutralize tebentafusp-tebn is unknown. The tebentafusp-tebn clearance increased in patients with high titer ADAs [see Clinical Pharmacology (12.3)]. Exploratory analyses with limited data suggest that formation of ADA does not appear to have clinically significant effect on frequency or severity of hypersensitivity related adverse reactions and no observed sign of decreased overall survival.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. KIMMTRAK is indicated for the treatment of HLA-A02:01-positive adult patients with unresectable or metastatic uveal melanoma.. KIMMTRAK is bispecific gp100 peptide-HLA-directed CD3 cell engager indicated for the treatment of HLA-A02:01-positive adult patients with unresectable or metastatic uveal melanoma (1, 2.1).

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Advise the patient to read the FDA-approved patient labeling (Patient Information).Cytokine Release Syndrome (CRS)Inform patients of the risk of CRS, and to immediately contact their healthcare provider for signs and symptoms associated with CRS (e.g., pyrexia, hypotension, hypoxia, chills, nausea, vomiting, fatigue, or headache) [see Warnings and Precautions (5.1)].Skin ReactionsInform patients that rashes and skin reactions have occurred in patients who have received KIMMTRAK. Advise patients to contact their healthcare provider for signs and symptoms of progressive or intolerable skin reactions [see Warnings and Precautions (5.2)].Elevated Liver Enzymes Inform patients that elevations in liver enzymes have occurred in patients who have received KIMMTRAK. Advise patients to contact their healthcare provider for signs and symptoms of liver toxicity (e.g., right sided abdominal pain, jaundice, scleral icterus) [see Warnings and Precautions (5.3)].Embryo-Fetal ToxicityAdvise females to inform their healthcare provider if they are pregnant or become pregnant. Inform females of the risk to fetus [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception while on KIMMTRAK and for week after the last dose [see Use in Specific Populations (8.1) and (8.3)]. LactationAdvise patients not to breastfeed during treatment with KIMMTRAK and for week after the last dose [see Use in Specific Populations (8.2)].Manufactured by:Immunocore Limited92 Park Drive, Milton ParkAbingdon, OxfordshireUnited Kingdom, OX144RYLicense no: 2239At:Baxter Oncology GmbHKantstrae 233790 Halle/WestfalenGermanyFor:Immunocore Commercial LLC181 Washington Street, Conshohocken, PA, US. Advise females to inform their healthcare provider if they are pregnant or become pregnant. Inform females of the risk to fetus [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception while on KIMMTRAK and for week after the last dose [see Use in Specific Populations (8.1) and (8.3)]. Advise patients not to breastfeed during treatment with KIMMTRAK and for week after the last dose [see Use in Specific Populations (8.2)].

LACTATION SECTION.

8.2 Lactation. Risk SummaryThere are no data on the presence of tebentafusp-tebn in human milk, the effect on the breastfed child, or the effects on milk production. Because tebentafusp-tebn may be excreted in human milk and because of the potential for serious adverse reactions in breastfed child, advise patients not to breastfeed during treatment with KIMMTRAK and for at least week after the last dose.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. Tebentafusp-tebn is bispecific gp100 peptide-HLA-A02:01 directed cell receptor CD3 cell engager. The TCR arm binds to gp100 peptide presented by human leukocyte antigen-A02:01 (HLA-A02:01) on the cell surface of uveal melanoma tumor cells.In vitro, tebentafusp-tebn bound to HLA-A02:01-positive uveal melanoma cells and activated polyclonal cells to release inflammatory cytokines and cytolytic proteins, which results in direct lysis of uveal melanoma tumor cells.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. No carcinogenicity or genotoxicity studies have been conducted with tebentafusp-tebn.No studies have been conducted to evaluate the effects of tebentafusp-tebn on fertility.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL NDC: 80446-401-01 100 mcg/0.5 mL Carton Label. 80446-401-01 100 mcg/0.5 mL Carton Label.

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. Lymphocyte counts declined the day after the first doses and returned to baseline prior to subsequent doses.Serum levels of cytokines (IFN-, TNF, IL-2, IL-6, IL-10 and IL-1RA) and chemokines (CXCL9, CXCL10, CXCL11, hepatocyte growth factor, and monocyte chemoattractant protein-1) were increased during the first three doses of KIMMTRAK with peak levels between to 24 hours after treatment with KIMMTRAK and levels returned to baseline prior to subsequent doses. In subsequent treatment cycles, cytokine elevation occurred in fewer patients with lesser intensity compared to the first doses.The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of KIMMTRAK have not been fully characterized.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. After single dose administration, tebentafusp-tebn Cmax and AUC0-7d increased in an approximately dose proportional manner from 20 to 68 mcg (0.3 to times the approved recommended dose). Following administration of the approved recommended dosage in patients with metastatic uveal melanoma, the steady-state geometric mean (% CV) Cmax of tebentafusp-tebn is 13 ng/mL (34.6%) and AUC0-7d is 4.6 ng.day/mL (23%) with no accumulation.DistributionTebentafusp-tebn geometric mean (% CV) steady-state volume of distribution is 7.56 (24%).EliminationThe geometric mean clearance of tebentafusp-tebn is 16.4 L/d (CV: 24.5%) and median terminal half-life is 7.5 hours (range: 6.8-7.5 hours).MetabolismTebentafusp-tebn is expected to be catabolized into small peptides and amino acids.Specific PopulationsNo clinically significant difference in the pharmacokinetics of tebentafusp-tebn were identified based on weight (43 to 163 kg), sex (48% female), age (23 to 91 years), or mild to moderate renal impairment based on creatinine clearance (CLcr) estimated by C-G formula (CLcr 30 to 89 mL/min) or mild hepatic impairment as measured by total bilirubin (TB) and aspartate aminotransferase (AST) (TB <= upper limit of normal (ULN) and AST ULN or TB 1 to 1.5x ULN and any AST).Tebentafusp-tebn has not been studied in patients with severe (CLcr 30 mL/min) renal impairment or in patients with moderate (TB >1.5 to 3x ULN, any AST) to severe (TB 3 to 10x ULN, any AST) hepatic impairment.ImmunogenicityMedian titer in the ADA-positive subgroup was 8192 across the 67 treatment cycles. The exposure (AUC0-7 days) of tebentafusp-tebn decreased by 97% and terminal half-life decreased to 10-14 minutes in patients with ADA titers greater than 8192.Drug InteractionElevation of certain proinflammatory cytokines may suppress CYP450 enzyme activities.

PREGNANCY SECTION.

8.1 Pregnancy. Risk Summary Based on the mechanism of action, KIMMTRAK may cause fetal harm when administered to pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data with KIMMTRAK in pregnant woman. No animal reproductive and developmental toxicity studies have been conducted with KIMMTRAK. Molecules of similar molecular weight can cross the placenta resulting in fetal exposure. Advise women of the potential risk to the fetus.In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.

SPL PATIENT PACKAGE INSERT SECTION.

This Patient Information has been approved by the U.S. Food and Drug Administration Issued: January 2022PATIENT INFORMATIONKIMMTRAK(R)(KIM-track)(tebentafusp-tebn)InjectionWhat is the most important information should know about KIMMTRAKKIMMTRAK can cause serious side effects that can be severe or, life threatening, and usually happens within the first three infusions. These side effects include:Cytokine Release Syndrome (CRS). Tell your healthcare provider right away if you get any of the following symptoms:fevertiredness or weaknessvomitingchillsnausealow blood pressure dizziness and light headednessheadachewheezing and trouble breathingrashYour healthcare provider will check for these problems during treatment with KIMMTRAK. Your healthcare provider may temporarily stop or completely stop your treatment with KIMMTRAK, if you have severe side effects.See What are the possible side effects of KIMMTRAK for more information about side effects.What is KIMMTRAKKIMMTRAK is prescription medicine used to treat HLA-A02:01-positive adults with uveal melanoma that cannot be removed by surgery or has spread.Your healthcare provider will test you for presence of HLA-A02:01 gene to make sure KIMMTRAK is right for you. It is not known if KIMMTRAK is safe and effective in children.Before you receive KIMMTRAK, tell your healthcare provider about all of your medical conditions, including if you:are pregnant or plan to become pregnant. KIMMTRAK may harm your unborn baby. Tell your healthcare provider if you become pregnant during treatment with KIMMTRAK.For females who are able to become pregnant:Your healthcare provider should do pregnancy test before you start treatment with KIMMTRAK.Use an effective form of birth control during treatment with KIMMTRAK and for at least week after the last dose of KIMMTRAK.are breastfeeding or plan to breastfeed. It is not known if KIMMTRAK passes into your breast milk. Do not breastfeed during the treatment with KIMMTRAK and for at least week after the last dose of KIMMTRAK.Tell your healthcare provider about all medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.How will receive KIMMTRAKKIMMTRAK will be given to you by intravenous (IV) infusion into your vein for 15 to 20 minutes.KIMMTRAK is usually given every week.Your healthcare provider will decide how many treatments you need.Your healthcare provider will keep you under observation for at least 16 hours following the first three KIMMTRAK treatments and for at least 30 minutes after future treatments.Your healthcare provider may delay your treatment of KIMMTRAK if you have certain side effects.Your healthcare provider may do blood tests regularly during treatment with KIMMTRAK.What are the possible side effects of KIMMTRAKKIMMTRAK can cause serious side effects, including:See What is the most important information should know about KIMMTRAK.Skin reactions. KIMMTRAK may cause skin reactions that require treatment. Tell your healthcare provider if you get symptoms of skin reactions, such as rash, itching, or skin swelling, that are severe and do not go away.Abnormal liver blood tests. Your healthcare provider will do blood tests to check your liver before you start KIMMTRAK and during treatment with KIMMTRAK. Tell your healthcare provider if you get symptoms of liver problems such as right-sided abdominal pain or yellowing of the skin or eyes.The most common side effects of KIMMTRAK include:cytokine release syndrome (CRS)rashfeveritchingtirednessnauseachillsstomach painswellinglow blood pressure (symptoms may include dizziness or light headedness)dry skinheadachevomitingabnormal liver blood testsThese are not all the possible side effects of KIMMTRAK.Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.General information about safe and effective use of KIMMTRAK.Medicines are sometimes prescribed for purposes other than those listed in Patient Information Leaflet. If you would like more information about KIMMTRAK, talk with your healthcare provider. You can ask your healthcare provider for more information about KIMMTRAK that is written for healthcare professionals.What are the ingredients in KIMMTRAKActive ingredient: tebentafuspInactive ingredients: citric acid monohydrate, di-sodium hydrogen phosphate, mannitol, polysorbate 20, trehalose, and Water for injection.Manufactured by:Immunocore Limited92 Park Drive, Milton ParkAbingdon, OxfordshireUnited Kingdom, OX144RYLicense no: 2239at: Baxter Oncology GmbH, Kantstrae 2, 33790 Halle/Westfalen Germany.For: Immunocore Commercial LLC 181 Washington Street Conshohocken, PA, USKIMMTRAK is trademark of the Immunocore LimitedFor more information, go to www.KIMMTRAK.com or call 1-844-IMMUNO1 (1-844-466-8661).. Cytokine Release Syndrome (CRS). Tell your healthcare provider right away if you get any of the following symptoms:fevertiredness or weaknessvomitingchillsnausealow blood pressure dizziness and light headednessheadachewheezing and trouble breathingrash. fever. tiredness or weakness. vomiting. chills. nausea. low blood pressure dizziness and light headedness. headache. wheezing and trouble breathing. rash. are pregnant or plan to become pregnant. KIMMTRAK may harm your unborn baby. Tell your healthcare provider if you become pregnant during treatment with KIMMTRAK.. Your healthcare provider should do pregnancy test before you start treatment with KIMMTRAK.. Use an effective form of birth control during treatment with KIMMTRAK and for at least week after the last dose of KIMMTRAK.. are breastfeeding or plan to breastfeed. It is not known if KIMMTRAK passes into your breast milk. Do not breastfeed during the treatment with KIMMTRAK and for at least week after the last dose of KIMMTRAK.. KIMMTRAK will be given to you by intravenous (IV) infusion into your vein for 15 to 20 minutes.. KIMMTRAK is usually given every week.. Your healthcare provider will decide how many treatments you need.. Your healthcare provider will keep you under observation for at least 16 hours following the first three KIMMTRAK treatments and for at least 30 minutes after future treatments.. Your healthcare provider may delay your treatment of KIMMTRAK if you have certain side effects.. Your healthcare provider may do blood tests regularly during treatment with KIMMTRAK.. See What is the most important information should know about KIMMTRAK.. Skin reactions. KIMMTRAK may cause skin reactions that require treatment. Tell your healthcare provider if you get symptoms of skin reactions, such as rash, itching, or skin swelling, that are severe and do not go away.. Abnormal liver blood tests. Your healthcare provider will do blood tests to check your liver before you start KIMMTRAK and during treatment with KIMMTRAK. Tell your healthcare provider if you get symptoms of liver problems such as right-sided abdominal pain or yellowing of the skin or eyes.. cytokine release syndrome (CRS). rash. fever. itching. tiredness. nausea. chills. stomach pain. swelling. low blood pressure (symptoms may include dizziness or light headedness). dry skin. headache. vomiting. abnormal liver blood tests.

SPL UNCLASSIFIED SECTION.

2.1 Patient Selection. Select patients for treatment of unresectable or metastatic uveal melanoma with KIMMTRAK based on positive HLA-A02:01 genotyping test [see Clinical Studies (14)]. An FDA-approved test for the detection of HLA-A02:01 genotyping is not currently available.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Risk Summary Based on the mechanism of action, KIMMTRAK may cause fetal harm when administered to pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data with KIMMTRAK in pregnant woman. No animal reproductive and developmental toxicity studies have been conducted with KIMMTRAK. Molecules of similar molecular weight can cross the placenta resulting in fetal exposure. Advise women of the potential risk to the fetus.In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.. 8.2 Lactation. Risk SummaryThere are no data on the presence of tebentafusp-tebn in human milk, the effect on the breastfed child, or the effects on milk production. Because tebentafusp-tebn may be excreted in human milk and because of the potential for serious adverse reactions in breastfed child, advise patients not to breastfeed during treatment with KIMMTRAK and for at least week after the last dose.. 8.3 Females and Males of Reproductive Potential. KIMMTRAK may cause fetal harm when administered to pregnant woman [see Use in Specific Populations (8.1)].Pregnancy TestingVerify pregnancy status in females of reproductive potential prior to initiating KIMMTRAK treatment.ContraceptionFemales Advise female of reproductive potential to use effective contraception during treatment and for week following the last dose of KIMMTRAK [see Use in Specific Populations (8.1)].. 8.4 Pediatric Use. Safety and efficacy of KIMMTRAK have not been established in pediatric patients.. 8.5 Geriatric Use. 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 years of age compared to younger adult patients.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Skin reactions: Rash, pruritus, and cutaneous edema occurred in patients treated with KIMMTRAK. If skin reactions occur, treat based on persistence and severity of symptoms (2.3, 5.2).Elevated liver enzymes: Elevations in liver enzymes occurred in patients treated with KIMMTRAK. Monitor ALT, AST, and total bilirubin (2.3, 5.3).Embryo-Fetal toxicity: May cause fetal harm. Advise patients of reproductive potential of the potential risk to the fetus and to use effective contraception (5.4, 8.1, 8.3).. Skin reactions: Rash, pruritus, and cutaneous edema occurred in patients treated with KIMMTRAK. If skin reactions occur, treat based on persistence and severity of symptoms (2.3, 5.2).. Elevated liver enzymes: Elevations in liver enzymes occurred in patients treated with KIMMTRAK. Monitor ALT, AST, and total bilirubin (2.3, 5.3).. Embryo-Fetal toxicity: May cause fetal harm. Advise patients of reproductive potential of the potential risk to the fetus and to use effective contraception (5.4, 8.1, 8.3).. 5.1 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 (6.1)]. Among patients who received KIMMTRAK, 23% received systemic corticosteroids for at least infusion, 8% received supplemental oxygen during at least infusion, and 0.8% received vasopressor for at least infusion. CRS led to permanent discontinuation in 1.2% of patients.In Study IMCg100-202, 60% of patients experienced >= Grade CRS with more than infusion, with the median number of events being (range - 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 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 (2.2)].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 (2.3)].. 5.2 Skin Reactions. Skin reactions, including rash, pruritus, 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 (44%) and Grade (21%) events. Skin reactions included rash (83%), pruritus (69%), erythema (25%), and cutaneous edema (27%) [see Adverse Reactions (6.1)].The median time to onset of skin reactions was day (range: - 55 days). The median time to improvement to <= Grade was approximately 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 (2.3)].. 5.3 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 infusions with KIMMTRAK. Most patients experiencing Grade or ALT/AST elevations had improvement to <= Grade within days. For events that were observed outside the setting of CRS, the median time to onset was 129 days. Grade or greater elevations in liver enzymes outside the setting of CRS occurred in approximately 8% of patients.Elevations in liver enzymes led to permanent discontinuation in 0.4% 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 (2.3)].. 5.4 Embryo-Fetal Toxicity. Based on the mechanism of action, KIMMTRAK may cause fetal harm when administered to pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with KIMMTRAK and for week after the last dose [see Use in Specific Populations (8.1, 8.3)].

RECENT MAJOR CHANGES SECTION.

Dosage and Administration (2.1) 11/2022.