BRIEF SUMMARY

TEBENTAFUSPTEBN- (Jan 2022)

Indctn- To treat  unresctable or metastatic unveal                                                                           melanoma   

Dosage- Injection: 100 mcg/0.5 mL solution in a single-dose vial-             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                                                                                                                      Dilute and administer by intravenous infusion over 15-20 minutes

ADR-  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 vomitingCI-

CI- None

WARNINGS--

 Skin reactions: Rash, pruritus, and cutaneous edema occurred in patients treated with the drug. If skin reactions occur, treat based on persistence and severity of symptoms

 Elevated liver enzymes: Elevations in liver enzymes occurred in patients treated with the drug. Monitor ALT, AST, and total bilirubin

  Embryo-Fetal toxicity: May cause fetal harm.

Pat Inform-

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)

 Skin Reactions- Inform patients that rashes and skin reactions have occurred in patients who have received the drug

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U.S. FDA APPROVED DRUGS SURING 2022                                        

Serial No 3

Name of the Drug-    KIMMTRAK

Active Ingredient -   Tebentafusptebn

Pharmacological Classification- To treat  unresctable or metastatic unveal                                                                           melanoma                                                                                                                                                                                                           Date of Approval-          1/25//22   

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use                    KIMMTRAK® safely and effectively.                                                                              See full prescribing information for KIMMTRAK® KIMMTRAK® (tebentafusp-tebn) injection, for intravenous use

Initial U.S. Approval: 2022

WARNING: CYTOKINE RELEASE SYNDROME-

Cytokine Release Syndrome (CRS), which may be serious or lifethreatening, occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours following first three infusions and then as clinically indicated

INDICATIONS AND USAGE-

KIMMTRAK is a bispecific gp100 peptide-HLA-directed CD3 T cell engager indicated for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma

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                                                                                                     

• Dilute and administer by intravenous infusion over 15-20 minutes

 • See Full Prescribing Information for instructions on preparation and administration of the diluted solution for intravenous infusion

 • Dosage interruption or permanent discontinuation may be required based on individual safety and tolerability 

 ADVERSE REACTIONS-

 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

 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 

 CONTRAINDICATIONS-                                                                                              None

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

 • Elevated liver enzymes: Elevations in liver enzymes occurred in patients treated with KIMMTRAK. Monitor ALT, AST, and total bilirubin

 • Embryo-Fetal toxicity: May cause fetal harm. Advise patients of reproductive potential of the potential risk to the fetus and to use effective contraception .

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                                                                                                     

• Dilute and administer by intravenous infusion over 15-20 minutes

 • See Full Prescribing Information for instructions on preparation and administration of the diluted solution for intravenous infusion

 • Dosage interruption or permanent discontinuation may be required based on individual safety and tolerability 

DOSAGE FORMS AND STRENGTHS-                                                                         Injection: 100 mcg/0.5 mL solution in a single-dose vial

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)

 Skin Reactions-                                                                                                       Inform 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

 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)

 Embryo-Fetal Toxicity                                                                                                      • Advise females to inform their healthcare provider if they are pregnant or become pregnant. Inform females of the risk to a fetus

 Use in Specific Populations                                                                                          . • Advise females of reproductive potential to use effective contraception while on KIMMTRAK and for 1 week after the last dose

 Lactation                                                                                                                           • Advise patients not to breastfeed during treatment with KIMMTRAK and for 1 week after the last dose 

 Manufactured by: Immunocore Limited 92 Park Drive, Milton Park Abingdon, Oxfordshire United Kingdom, OX144RY License no: xxxxx At: Baxter Oncology GmbH Kantstraße 2 33790 Halle/Westfalen Germany For: Immunocore Commercial LLC 181 Washington Street, Conshohocken, PA, US

CLINICAL PHARMACOLOGY

1. Mechanism of Action-                                                                                            Tebentafusp-tebn is a bispecific gp100 peptide-HLA-A*02:01 directed T cell receptor CD3 T cell engager.

2. Pharmacodynamics -                                                                                           Lymphocyte counts declined the day after the first 3 doses and returned to baseline prior to subsequent doses.                                                                                                 Serum levels of cytokines (IFN-?, TNFa, 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 8 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 3 doses.

The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of KIMMTRAK have not been fully characterized.

3 Pharmacokinetics-                                                                                                          After a single dose administration, tebentafusp-tebn Cmax and AUC0-7d increased in an approximately dose proportional manner from 20 to 68 mg (0.3 to 1 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. 

Distribution-                                                                                                            Tebentafusp-tebn geometric mean (% CV) steady-state volume of distribution is 7.56 L (24%).

Elimination-                                                                                                                   The 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). Metabolism Tebentafusp-tebn is expected to be catabolized into small peptides and amino acids.

Specific Populations-                                                                                                    No 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.

Immunogenicity-                                                                                                               Median 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 Interaction Elevation of certain proinflammatory cytokines may suppress CYP450 enzyme activities.

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary-                                                                                         Based on the mechanism of action, KIMMTRAK may cause fetal harm when administered to a pregnant woman

 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.

2. Lactation-                                                                                                                 Risk Summary-  There 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 a breastfed child, advise patients not to breastfeed during treatment with KIMMTRAK and for at least 1 week after the last dose.

3. Females and Males of Reproductive Potential-                                                     KIMMTRAK may cause fetal harm when administered to a pregnant woman

 Pregnancy Testing -                                                                                                 Verify pregnancy status in females of reproductive potential prior to initiating KIMMTRAK treatment.

Contraception Females -                                                                                             Advise female of reproductive potential to use effective contraception during treatment and for 1 week following the last dose of KIMMTRAK

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

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.