b'IMJUDO (tremelimumab-actl) injection, for intravenous use 3hepatic failure (0.5%), and immune-mediated hepatitis (0.5%). TheTable 6. Laboratory Abnormalities Worsening from BaselinetheagentsadministeredincombinationwithIMJUDOfor most common adverse reactions (occurring in20% of patients)Occurring in20% of Patients in the HIMALAYA study (contd) recommended contraception duration, as appropriate.were rash, diarrhea, fatigue, pruritus, musculoskeletal pain, andIMJUDO andSorafenib Pediatric Useabdominal pain. Durvalumab The safety and effectiveness of tremelimumab-actl have not Permanent discontinuation of the treatment regimen due to anLaboratoryAny grade 1Grade 3 1Any grade 1Grade 3 1 been established in pediatric patients.adverse reaction occurred in 14% of patients; the most commonAbnormality (%) 2 or 4 (%) 2 or 4 Geriatric Useadverse reactions leading to treatment discontinuation ( 1%) were(%) 2 (%) 2 Ofthe393patientswithuHCCtreatedwithIMJUDOin hemorrhage (1.8%), diarrhea (1.5%), AST increased (1%), and hepatitis (1%). Hematology combination with durvalumab, 50% of patients were 65 years Dosage interruptions or delay of the treatment regimen due to anHemoglobin 52 4.8 40 6 or older and 13% of patients were 75 years or older. No overall adverse reaction occurred in 35% of patients. Adverse reactionsdecreased differences in safety or efficacy of IMJUDO have been observed which required dosage interruption or delay in1% of patientsLymphocytes 41 11 39 10 between patients 65 years or older and younger adult patients.includedALTincreased(3.6%),diarrhea(3.6%),rash(3.6%),decreased PATIENT COUNSELING INFORMATIONamylase increased (3.4%), AST increased (3.1%), lipase increasedPlatelets decreased 29 1.6 35 3.1 Advise the patient to read the FDA-approved patient labeling (2.8%),pneumonia(1.5%),hepatitis(1.5%),pyrexia(1.5%),Leukocytes 20 0.8 30 1.1 (see Medication Guide in the full Prescribing Information).anemia (1.3%), thrombocytopenia(1%), hyperthyroidism (1%),decreased Immune-Mediated Adverse Reactionspneumonitis (1%), and blood creatinine increased (1%). 1 Inform patients of the risk of immune-mediated adverse reactions Table 5 summarizes the adverse reactions that occurred in patients2Graded according to NCI CTCAE version 4.03. thatmayrequirecorticosteroidtreatmentandinterruptionor treatedwithIMJUDOincombinationwithdurvalumabinthe Each test incidence is based on the number of patients who had bothdiscontinuationofIMJUDOincombinationwithdurvalumab, baseline and at least one on-study laboratory measurement available: HIMALAYA study. IMJUDO with durvalumab (range: 367-378) and sorafenib (range: 344-352). including[seeWarningsandPrecautions(5.1)inthefull Table 5. Adverse Reactions Occurring in10% Patients in thePrescribing Information]:HIMALAYA study USE IN SPECIFIC POPULATIONS Pneumonitis:Advisepatientstocontacttheirhealthcare IMJUDO andSorafenib Pregnancy provider immediately for any new or worsening cough, chest Durvalumab (N=374) Risk summary pain, or shortness of breath.(N=388) Based on findings from animal studies and its mechanism ofColitis: Advise patients to contact their healthcare provider All Grades Grade 3-4 All Grades Grade 3-4action, IMJUDO can cause fetal harm when administered to aimmediately for diarrhea, blood or mucus in stools, or severe Adverse Reaction (%) (%) (%) (%) pregnant woman [see Clinical Pharmacology (12.1) in the fullabdominal pain.Prescribing Information]. There are no available data on the use ofHepatitis: Advise patients to contact their healthcare provider Gastrointestinal disorders IMJUDO in pregnant women. In animal studies, CTLA-4 blockadeimmediately for jaundice, severe nausea or vomiting, pain on Diarrhea 1 27 6 45 4.3 is associated with increased risk of immune-mediated rejection ofthe right side of abdomen, lethargy, or easy bruising or bleeding.Abdominal pain 1 20 1.8 24 4 the developing fetus and fetal death (see Data). Endocrinopathies: Advise patients to contact their healthcare Nausea 12 0 14 0 Human immunoglobulin G2 (IgG2) is known to cross the placentalprovider immediately for signs or symptoms of hypothyroidism, Skin and subcutaneous tissue disorders barrier; therefore, IMJUDO has the potential to be transmitted fromhyperthyroidism,adrenalinsufficiency,type1diabetes 1 the mother to the developing fetus. Advise pregnant women andmellitus, or hypophysitis.Rash 32 2.8 57 12 females of reproductive potential of the potential risk to a fetus. Nephritis: Advise patients to contact their healthcare provider Pruritus 23 0 6 0.3 In the U.S. general population, the estimated background riskimmediately for signs or symptoms of nephritis.Metabolism and nutrition disorders of major birth defects and miscarriage in clinically recognizedDermatological Reactions: Advise patients to contact their Decreased appetite 17 1.3 18 0.8 pregnancies is 2% to 4% and 15% to 20%, respectively. healthcare provider immediately for signs or symptoms of General disorders and administration site conditions Data severe dermatological reactions.Pancreatitis:Advisepatientstocontacttheirhealthcare Fatigue 1 26 3.9 30 6 Animal Data provider immediately for signs or symptoms of pancreatitis.Pyrexia 1 13 0.3 9 0.3 Inareproductionstudy,administrationoftremelimumab-actlOther Immune-Mediated Adverse Reactions: Advise patients Psychiatric disorders to pregnant cynomolgus monkeys during the period of organo-to contact their healthcare provider immediately for signs or genesis was not associated with maternal toxicity or effects onsymptoms of aseptic meningitis, immune thrombocytopenia, Insomnia 10 0.3 4.3 0 embryo-fetaldevelopmentatexposurelevelsapproximatelymyocarditis, hemolytic anemia, myositis, uveitis, keratitis, and Endocrine disorders 4 to 31-times higher than those observed at a recommended dosemyasthenia gravis.Hypothyroidism 1 14 0 6 0 range of 75 mg to 300 mg based on area under the curve (AUC).Infusion-Related Reactions:CTLA-4 plays a role in maintaining maternal immune tolerance Musculoskeletal and Connective Tissue Disorders to the fetus to preserve pregnancy and in immune regulation ofAdvise patients to contact their healthcare provider immediately Musculoskeletal22 2.6 17 0.8 the newborn. In a murine model of pregnancy, CTLA-4 blockadeforsignsorsymptomsofinfusion-relatedreactions[see pain 1 resulted in increased resorptions and reduced live fetuses. MatedWarningsandPrecautions(5.2)inthefullPrescribing 1 genetically engineered mice heterozygous for CTLA-4 (CTLA-4+/-)Information]. Represents a composite of multiple related terms. gave birth to CTLA-4+/- offspring and offspring deficient in CTLA-4Embryo-Fetal Toxicity:Table 6 summarizes the laboratory abnormalities that occurred(homozygous negative, CTLA-4-/-) that appeared healthy at birth.AdvisefemalesofreproductivepotentialthatIMJUDO in patients treated with IMJUDO in combination with durvalumabThe CTLA-4-/- homozygous negative offspring developed signs ofcan cause harm to a fetus and to inform their healthcare in the HIMALAYA study. a lymphoproliferative disorder and died by 3 to 4 weeks of ageprovider of a known or suspected pregnancy [see Warnings Table 6. Laboratory Abnormalities Worsening from Baselinewith multiorgan tissue destruction. Based on its mechanism ofand Precautions (5.3) and Use in Specific Populations (8.1, Occurring in20% of Patients in the HIMALAYA study action, fetal exposure to tremelimumab-actl may increase the risk8.3) in the full Prescribing Information].of developing immune-mediated disorders or altering the normalAdvisefemalesofreproductivepotentialtouseeffective IMJUDO andSorafenib immune response. contraception during treatment and for 3 months after the last Durvalumab Lactation dose of IMJUDO [see Use in Specific Populations (8.3) in the LaboratoryAny grade 1Grade 3 1Any grade 1Grade 3 1 Risk Summary full Prescribing Information].Abnormality (%) 2 or 4 (%) 2 or 4 There are no data on the presence of tremelimumab-actl in humanLactation:(%) 2 (%) 2 milk, its effects on a breastfed child, or on milk production.Advise female patients not to breastfeed while taking IMJUDO Chemistry Maternal IgG is known to be present in human milk. The effectsand for 3 months after the last dose [see Warnings and Aspartate 63 27 55 21 of local gastrointestinal exposure and limited systemic exposurePrecautions (5.3) and Use in Specific Populations (8.2) in the Aminotransferasein the breastfed child to IMJUDO are unknown. Because of thefull Prescribing Information].increased potential for serious adverse reactions in the breastfed child, Alanine 56 18 53 12 advise women not to breastfeed during treatment with IMJUDOManufactured for: AstraZeneca Pharmaceuticals LP Aminotransferaseand for 3 months after the last dose. Refer to the PrescribingWilmington, DE 19850increased Information for agents administered in combination with IMJUDOManufactured By: AstraZeneca AB, Sdertlje, Sweden SE-15185Sodium decreased 46 15 40 11 for breastfeeding recommendations, as appropriate. US License No. 2059Bilirubin increased 41 8 47 11 Females and Males of Reproductive Potential Alkaline 41 8 44 5 IMJUDO can cause fetal harm when administered to a pregnantIMJUDOis a registered trademark of the AstraZeneca groupPhosphatase woman[seeUseinSpecificPopulations(8.1)inthefullof companies.increased Prescribing Information]. AstraZeneca 2022Glucose increased 39 14 29 4 Pregnancy Testing 06/23 US-77951 7/23Calcium decreased 34 0 43 0.3 Verifypregnancystatusoffemalesofreproductivepotential prior to initiating treatment with IMJUDO. Albumin decreased 31 0.5 37 1.7 ContraceptionPotassium 28 3.8 21 2.6 Advisefemalesofreproductivepotentialtouseeffective increased contraception during treatment with IMJUDO and for 3 months Creatinine increased 21 1.3 15 0.9 afterthelastdose.RefertothePrescribingInformationfor US-76417_US-77669_US-77951 Imfinzi-Imjudo US Medicine - The Compendium.indd 9 12/6/23 3:45 PM'