b'IMFINZI (durvalumab) injection, for intravenous use 3including Grade 3 (0.5%) adverse reactions. Systemic cortico-IMFINZI with Tremelimumab-actl Immune-MediatedAdverseReactions[seeWarningsand steroids were required in 2 patients (2/51) and all patients requiredImmune-mediated pancreatitis occurred in 2.3% (9/388) of patientsPrecautions (5.1) in the full Prescribing Information].endocrine therapy. receiving IMFINZI in combination with tremelimumab-actl, including Infusion-RelatedReactions[seeWarningsandPrecautions Type 1 Diabetes Mellitus, which can present with diabetic ketoacidosis Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions. Events (5.2) in the full Prescribing Information].Monitor patients for hyperglycemia or other signs and symptoms ofresolved in 6 of the 9 patients. Systemic corticosteroids wereClinical Trials Experience diabetes. Initiate treatment with insulin as clinically indicated. With- required in all 9 patients and of these 7 patients required high-doseBecauseclinicaltrialsareconductedunderwidelyvarying hold or permanently discontinue IMFINZI based on the severity [seecorticosteroid treatment (at least 40 mg prednisone or equivalentconditions, adverse reaction rates observed in the clinical trials of Dosage and Administration (2.2) in the full Prescribing Information]. per day). a drug cannot be directly compared to rates in the clinical trials of IMFINZI as a Single Agent Other Immune-Mediated Adverse Reactions another drug and may not reflect the rates observed in practice.Grade 3 immune-mediated type 1 diabetes mellitus occurred inThefollowingclinicallysignificant,immune-mediatedadverseThe data described in the Warnings and Precautions section reflect 0.1%(1/1889)ofpatientsreceivingIMFINZI.Thispatientreactionsoccurredatanincidenceoflessthan1%eachinexposure to IMFINZI as a single agent in a total of 1889 patients required long-term insulin therapy and IMFINZI was permanentlypatients who received IMFINZI or IMFINZI in combination withenrolled in the PACIFIC study (a randomized, placebo-controlled discontinued. Two additional patients (0.1%, 2/1889) had eventstremelimumab-actl, or were reported with the use of other PD-1/ study that enrolled 475 patients with Stage III NSCLC), Study 1108 of hyperglycemia requiring insulin therapy that did not resolve atPD-L1 blocking antibodies. (anopen-label,single-arm,multicohortstudythatenrolled the time of reporting. Cardiac/vascular: Myocarditis, pericarditis, vasculitis. 970patientswithadvancedsolidtumors),andanadditional IMFINZI with Tremelimumab-actl Nervous system: Meningitis, encephalitis, myelitis and demyelination,open-label,single-armtrial(ATLANTICStudy)thatenrolled Two patients (0.5%, 2/388) had events of hyperglycemia requiringmyasthenic syndrome/myasthenia gravis (including exacerbation),444 patients with advanced solid tumors, including NSCLC. In insulin therapy that had not resolved at last follow-up. Guillain-Barr syndrome, nerve paresis, autoimmune neuropathy. these trials, IMFINZI was administered at a dose of 10 mg/kg Ocular: Uveitis, iritis, and other ocular inflammatory toxicities canevery 2 weeks. Among the 1889 patients, 38% were exposed IMFINZI with Tremelimumab-actl and Platinum-Based Chemotherapy occur. Some cases can be associated with retinal detachment.for 6 months or more and 18% were exposed for 12 months or Immune-mediated Type 1 diabetes mellitus occurred in 0.5% (3/596)Variousgradesofvisualimpairmenttoincludeblindnesscanmore. The data also reflect exposure to IMFINZI in combination of patients receiving IMFINZI in combination with tremelimumab-occur. If uveitis occurs in combination with other immune-mediated withchemotherapyin265patientsfromtheCASPIANstudy actl,includingGrade3(0.3%)adversereactions.Allpatientsadversereactions,consideraVogt-Koyanagi-Harada-like(a randomized, open-label study in patients with ES-SCLC), in required endocrine therapy. syndrome, as this may require treatment with systemic steroids338 patients from the TOPAZ-1 study (a randomized, double-Immune-Mediated Nephritis with Renal Dysfunction to reduce the risk of permanent vision loss. blind study in patients with BTC). In the CASPIAN and TOPAZ-1 IMFINZI can cause immune-mediated nephritis. studies, IMFINZI was administered at a dose of 1,500 mg every Gastrointestinal: Pancreatitis including increases in serum amylase3 or 4 weeks.IMFINZI as a Single Agent and lipase levels, gastritis, duodenitis. The data described in the Warnings and Precautions also reflect Immune-mediated nephritis occurred in 0.5% (10/1889) of patientsMusculoskeletalandconnectivetissuedisorders:Myositis/ exposure to IMFINZI 1,500 mg in combination with tremelimumab-receiving IMFINZI, including Grade 3 ( 0.1%) adverse reactions.polymyositis, rhabdomyolysis and associated sequelae includingactl 300 mg in 388 patients in HIMALAYA. In the HIMALAYA Events resolved in 5 of the 10 patients and resulted in permanentrenal failure, arthritis, polymyalgia rheumatic. study patients received IMFINZI 1,500 mg in combination with discontinuationin3patients.SystemiccorticosteroidswereEndocrine: Hypoparathyroidism. tremelimumab-actl as a single intravenous infusion of 300 mg, required in all patients with immune-mediated nephritis. Other (hematologic/immune): Hemolytic anemia, aplastic anemia,followed by IMFINZI 1,500 mg every 4 weeks. The pooled safety IMFINZI with Tremelimumab-actl hemophagocyticlymphohistiocytosis,systemicinflammatorypopulation (N = 596) described in the Warnings and Precautions Immune-mediated nephritis occurred in 1% (4/388) of patientsresponse syndrome, histiocytic necrotizing lymphadenitis (Kikuchisection reflect exposure to IMFINZI 1,500 mg in combination receivingIMFINZIincombinationwithtremelimumab-actl,lymphadenitis),sarcoidosis,immunethrombocytopenia,solidwithtremelimumab-actl75mgandhistology-basedplatinum including Grade 3 (0.5%) adverse reactions. Events resolved inorgan transplant rejection. chemotherapyregimensin330patientsinPOSEIDON[see 3 of the 4 patients and resulted in permanent discontinuation inInfusion-Related Reactions Clinical Studies (14.1) in the full Prescribing Information] and 2 patients. Systemic corticosteroids were required in all patients266patientswithES-SCLCinCASPIANwhoreceivedupto withimmune-mediatednephritis;ofthese,3patientsrequiredIMFINZIcancausesevereorlife-threateninginfusion-relatedfour cycles of platinum-etoposide plus IMFINZI 1,500 mg with high-dose corticosteroid treatment (at least 40 mg prednisone orreactions. tremelimumab-actl 75 mg every 3 weeks followed by IMFINZI equivalent per day). Monitor for signs and symptoms of infusion-related reactions.1,500 mg every 4 weeks (an unapproved regimen for extensive IMFINZI with Tremelimumab-actl and Platinum-Based Chemotherapy Interrupt, slow the rate of, or permanently discontinue IMFINZIstage small cell lung cancer). Among the 596 patients, 55% were Immune-mediated nephritis occurred in 0.7% (4/596) of patientsbased on the severity [see Dosage and Administration (2.2) in exposed to IMFINZI for 6 months or more and 24% were exposed receiving IMFINZI in combination with tremelimumab-actl, includingthe full Prescribing Information]. For Grade 1 or 2 infusion-relatedfor 12 months or more.Grade 3 (0.2%) adverse reactions. Events resolved in 1 of thereactions, consider using pre-medications with subsequent doses. The data described in this section reflect exposure to IMFINZI in 4 patients and resulted in permanent discontinuation in 3 patients.IMFINZI as a Single Agent patients with Stage III NSCLC enrolled in the PACIFIC study, in SystemiccorticosteroidswererequiredinallpatientswithInfusion-related reactions occurred in 2.2% (42/1889) of patientspatients with metastatic NSCLC enrolled in the POSEIDON study, immune-mediated nephritis. receiving IMFINZI, including Grade 3 (0.3%) adverse reactions. in patients with ES-SCLC enrolled in the CASPIAN study, in patients Immune-Mediated Dermatology Reactions IMFINZI in Combination with Tremelimumab-actl with BTC enrolled in the TOPAZ-1 study and in patients with IMFINZI can cause immune-mediated rash or dermatitis. ExfoliativeInfusion-related reactions occurred in 10 (2.6%) patients receivinguHCC included in the HIMALAYA study.dermatitis, including Stevens Johnson Syndrome (SJS), drug rashIMFINZI in combination with tremelimumab-actl. Hepatocellular Carcinomawitheosinophiliaandsystemicsymptoms(DRESS),andtoxicIMFINZI with Tremelimumab-actl and Platinum-Based Chemotherapy Unresectable HCC - HIMALAYAepidermal necrolysis (TEN), has occurred with PD-1/L-1 blockingInfusion-related reactions occurred in 2.9% (17/596) of patientsThe safety of IMFINZI in combination with tremelimumab-actl was antibodies. Topical emollients and/or topical corticosteroids may bereceiving IMFINZI in combination with tremelimumab-actl, includingevaluated in a total of 388 patients with uHCC in HIMALAYA, a adequate to treat mild to moderate non-exfoliative rashes. WithholdGrade 3 (0.3%) adverse reactions. randomized, open-label, multicenter study [see Clinical Studies or permanently discontinue IMFINZI depending on severity [see (14.1)inthefullPrescribingInformation].PatientsreceivedDosage and Administration (2.2) in the full Prescribing Information]. Complications of Allogeneic HSCT after IMFINZI IMFINZI 1,500 mg administered as a single intravenous infusion IMFINZI as a Single Agent Fatal and other serious complications can occur in patients whoin combination with tremelimumab-actl 300 mg on the same day, Immune-mediated rash or dermatitis occurred in 1.8% (34/1889)receive allogeneic hematopoietic stem cell transplantation (HSCT)followed by IMFINZI every 4 weeks or sorafenib 400 mg given of patients receiving IMFINZI, including Grade 3 (0.4%) adversebefore or after being treated with a PD-1/L-1 blocking antibody.orally twice daily.reactions. Events resolved in 19 of the 34 patients and resulted inTransplant-related complications include hyperacute graft-versus- Serious adverse reactions occurred in 41% of patients who received permanent discontinuation in 2 patients. Systemic corticosteroidshost-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-IMFINZI in combination with tremelimumab-actl. Serious adverse were required in all patients with immune-mediated rash or dermatitis. occlusive disease (VOD) after reduced intensity conditioning, andreactions in 1% of patients included hemorrhage (6%), diarrhea steroid-requiring febrile syndrome (without an identified infectious(4%), sepsis (2.1%), pneumonia (2.1%), rash (1.5%), vomiting IMFINZI with Tremelimumab-actl cause). These complications may occur despite intervening therapy(1.3%), acute kidney injury (1.3%), and anemia (1.3%). Fatal Immune-mediated rash or dermatitis occurred in 4.9% (19/388) ofbetween PD-1/L-1 blockade and allogeneic HSCT. adversereactionsoccurredin8%ofpatientswhoreceived patients receiving IMFINZI in combination with tremelimumab-actl,Followpatientscloselyforevidenceoftransplant-relatedIMFINZI in combination with tremelimumab-actl, including death including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions.complications and intervene promptly. Consider the benefit versus(1%),hemorrhageintracranial(0.5%),cardiacarrest(0.5%), Events resolved in 13 of the 19 patients and resulted in permanentrisks of treatment with a PD-1/L-1 blocking antibody prior to or afterpneumonitis (0.5%), hepatic failure (0.5%), and immune-mediated discontinuationin2patients.Systemiccorticosteroidswerean allogeneic HSCT. hepatitis (0.5%). The most common adverse reactions (occurring required in all patients with immune-mediated rash or dermatitis;Embryo-Fetal Toxicity in20%ofpatients)wererash,diarrhea,fatigue,pruritis, of these, 12 patients required high-dose corticosteroid treatmentBased on its mechanism of action and data from animal studies,musculoskeletal pain, and abdominal pain.(at least 40 mg prednisone or equivalent per day). One patientIMFINZI can cause fetal harm when administered to a pregnantPermanent discontinuation of treatment regimen due to an adverse received other immunosuppressants. woman.Inanimalreproductionstudies,administrationofreaction occurred in 14% of patients; the most common adverse IMFINZI with Tremelimumab-actl and Platinum-Based Chemotherapy durvalumab to cynomolgus monkeys from the onset of organo-reactionsleadingtotreatmentdiscontinuation(1%)were Immune-mediated rash or dermatitis occurred in 7.2% (43/596) ofgenesis through delivery resulted in increased premature delivery,hemorrhage (1.8%), diarrhea (1.5%), AST increased (1%), and patients receiving IMFINZI in combination with tremelimumab-actl,fetal loss and premature neonatal death. Advise pregnant women ofhepatitis (1%).including Grade 3 (0.3%) adverse reactions. Events resolved inthe potential risk to a fetus. Advise females of reproductive potentialDosage interruptions or delay of the treatment regimen due to an 32 of the 43 patients and resulted in permanent discontinuation into use effective contraception during treatment with IMFINZI and foradverse reaction occurred in 35% of patients. Adverse reactions 2 patients. Systemic corticosteroids were required in all patients3 months after the last dose of IMFINZI [see Use in Specificwhich required dosage interruption or delay in1% of patients with immune-mediated rash or dermatitis. Populations (8.1, 8.3) in the full Prescribing Information]. includedALTincreased(3.6%),diarrhea(3.6%),rash(3.6%), Immune-Mediated Pancreatitis ADVERSE REACTIONS amylase increased (3.4%), AST increased (3.1%), lipase increased IMFINZIincombinationwithtremelimumab-actlcancauseThe following adverse reactions are discussed in greater detail in(2.8%),pneumonia(1.5%),hepatitis(1.5%),pyrexia(1.5%), immune-mediated pancreatitis. other sections of the labeling. anemia (1.3%), thrombocytopenia (1%), hyperthyroidism (1%), pneumonitis (1%), and blood creatinine increased (1%).US-76417_US-77669_US-77951 Imfinzi-Imjudo US Medicine - The Compendium.indd 5 12/6/23 3:45 PM'