b'IMJUDO (tremelimumab-actl) injection, for intravenous use 222 of the 23 patients and resulted in permanent discontinuationEvents resolved in 5 of the 42 patients. One patient receivedInfusion-Related Reactionsin 5 patients. All patients received systemic corticosteroids, andhigh-dose corticosteroid treatment (at least 40 mg prednisoneIMJUDO in combination with durvalumab can cause severe or 20 of the 23 patients received high-dose corticosteroid treatmentorequivalentperday).Allpatientsrequiredothertherapylife-threatening infusion-related reactions.(at least 40 mg prednisone or equivalent per day). Three patients(thiamazole, carbimazole, propylthiouracil, perchlorate, calciumMonitor for signs and symptoms of infusion-related reactions. also received other immunosuppressants. channel blocker, or beta-blocker). Interrupt, slow the rate of, or permanently discontinue IMJUDO and Intestinal perforation has been observed in other studies of IMJUDOType1DiabetesMellitus,WhichCanPresentwithDiabeticdurvalumab based on the severity [see Dosage and Administration in combination with durvalumab. Ketoacidosis: Monitor patients for hyperglycemia or other signs and(2.2)inthefullPrescribingInformation].ForGrade1or2 Immune-Mediated Hepatitis symptoms of diabetes. Initiate treatment with insulin as clinicallyinfusion-relatedreactions,considerusingpre-medicationswith IMJUDOincombinationwithdurvalumabcancauseimmune-indicated.WithholdorpermanentlydiscontinueIMJUDOinsubsequent doses.mediated hepatitis, which may be fatal. combination with durvalumab based on the severity [see DosageIMJUDO with DurvalumabIMJUDO with Durvalumab and Administration (2.2) in the full Prescribing Information]. Infusion-related reactions occurred in 10 (2.6%) patients receiving Immune-mediated hepatitis occurred in 7.5% (29/388) of patientsIMJUDO with Durvalumab IMJUDO in combination with durvalumab.receiving IMJUDO in combination with durvalumab, includingTwo patients (0.5%, 2/388) had events of hyperglycemia requiringIMJUDO with Durvalumab and Platinum-Based Chemotherapyfatal(0.8%),Grade4(0.3%),andGrade3(4.1%)adverseinsulin therapy that had not resolved at last follow-up. Infusion-related reactions occurred in 2.9% (17/596) of patients reactions. Events resolved in 12 of the 29 patients and resulted inImmune-Mediated Nephritis with Renal Dysfunction receiving IMJUDO in combination with durvalumab and platinum- permanent discontinuation in 9 patients. Systemic corticosteroidsIMJUDOincombinationwithdurvalumabcancauseimmune-based chemotherapy, including Grade 3 (0.3%) adverse reactions.were required in all 29 patients and all 29 patients required high-dosemediated nephritis. Embryo-Fetal Toxicitycorticosteroid treatment (at least 40 mg prednisone or equivalentIMJUDO with Durvalumab Based on findings from animal studies and its mechanism of action, per day). Eight patients (8/29) required other immunosuppressants. Immune-mediatednephritisoccurredin1%(4/388)ofpatientsIMJUDO can cause fetal harm when administered to a pregnant Immune-Mediated Endocrinopathies receiving IMJUDO in combination with durvalumab, including Grade 3woman. In animal studies, CTLA-4 blockade is associated with Adrenal Insufficiency: IMJUDO in combination with durvalumab(0.5%) adverse reactions. Events resolved in 3 of the 4 patientshigher incidence of pregnancy loss.can cause primary or secondary adrenal insufficiency. For Grade 2and resulted in permanent discontinuation in 2 patients. SystemicAdvise pregnant women and females of reproductive potential of the orhigheradrenalinsufficiency,initiatesymptomatictreatment,corticosteroids were required in all patients with immune-mediatedpotential risk to a fetus. Advise females of reproductive potential to including hormone replacement as clinically indicated. Withhold ornephritis; of these, 3 patients required high-dose corticosteroiduse effective contraception during treatment with IMJUDO and for permanently discontinue IMJUDO in combination with durvalumabtreatment (at least 40 mg prednisone or equivalent per day). 3 months after the last dose of IMJUDO [see Use in Specific based on the severity [see Dosage and Administration (2.2) in theImmune-Mediated Dermatology Reactions Populations (8.1, 8.3) in the full Prescribing Information].full Prescribing Information]. IMJUDO in combination with durvalumab can cause immune-ADVERSE REACTIONSIMJUDO with Durvalumab mediatedrashordermatitis.Exfoliativedermatitis,includingThe following adverse reactions are discussed in greater detail in Immune-mediated adrenal insufficiency occurred in 1.5% (6/388)Stevens Johnson Syndrome (SJS), drug rash with eosinophiliaother sections of the labeling.of patients receiving IMJUDO in combination with durvalumab,and systemic symptoms (DRESS), and toxic epidermal necrolysisImmune-MediatedAdverseReactions[seeWarningsand including Grade 3 (0.3%) adverse reactions. Events resolved in(TEN),hasoccurredwithCTLA-4andPD-1/L-1blockingPrecautions (5.1) in the full Prescribing Information].2 of the 6 patients. Systemic corticosteroids were required in all 6antibodies.Topicalemollientsand/ortopicalcorticosteroidsInfusion-Related Reactions [see Warnings and Precautions patients, and of these, 1 patient required high-dose corticosteroidmaybeadequatetotreatmildtomoderatenon-exfoliative(5.2) in the full Prescribing Information].treatment (at least 40 mg prednisone or equivalent per day). rashes.WithholdorpermanentlydiscontinueIMJUDOin Hypophysitis:IMJUDOincombinationwithdurvalumabcancombination with durvalumab depending on severity [see DosageClinical Trials Experiencecause immune-mediated hypophysitis. Hypophysitis can presentand Administration (2.2) in the full Prescribing Information]. Becauseclinicaltrialsareconductedunderwidelyvarying withacutesymptomsassociatedwithmasseffectsuchasIMJUDO with Durvalumab conditions, adverse reaction rates observed in clinical trials of a headache, photophobia, or visual field cuts. Hypophysitis can causeImmune-mediated rash or dermatitis occurred in 4.9% (19/388)drug cannot be directly compared to rates in the clinical trials of hypopituitarism. Initiate symptomatic treatment including hormoneof patients receiving IMJUDO in combination with durvalumab,another drug and may not reflect the rates observed in practice.replacementasclinicallyindicated.Withholdorpermanentlyincluding Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions.ThedatadescribedintheWarningsandPrecautionsreflect discontinue IMJUDO in combination with durvalumab dependingEvents resolved in 13 of the 19 patients and resulted in permanentexposure to IMJUDO 300 mg in combination with durvalumab onseverity[seeDosageandAdministration(2.2)inthefulldiscontinuationin2patients.Systemiccorticosteroidswere1,500 mg in 388 patients in HIMALAYA. In the HIMALAYA study Prescribing Information]. required in all patients with immune-mediated rash or dermatitis;patientsreceivedIMJUDO300mgadministeredasasingle IMJUDO with Durvalumab of these, 12 patients required high-dose corticosteroid treatmentintravenous infusion in combination with durvalumab 1,500 mg on Immune-mediatedhypophysitis/hypopituitarismoccurredin(at least 40 mg prednisone or equivalent per day). One patientthe same day, followed by durvalumab every 4 weeks.1% (4/388) of patients receiving IMJUDO in combination withreceived other immunosuppressants. The data also reflects exposure to IMJUDO 75 mg in combination durvalumab. Events resolved in 2 of the 4 patients. SystemicImmune-Mediated Pancreatitis withdurvalumab1,500mgandhistology-basedplatinum corticosteroids were required in 3 patients, and of these, 1 patientIMJUDOincombinationwithdurvalumabcancauseimmune-chemotherapy regimens in the pooled safety population (N=596) receivedhigh-dosecorticosteroidtreatment(atleast40mgmediated pancreatitis. of 330 patients in POSEIDON [see Clinical Studies (14.1) in the prednisone or equivalent per day). Two patients also requiredfull Prescribing Information], and 266 patients in CASPIAN who endocrine therapy. IMJUDO with Durvalumab received up to four cycles of platinum-etoposide plus durvalumab Thyroid Disorders: IMJUDO in combination with durvalumab canImmune-mediated pancreatitis occurred in 2.3% (9/388) of patients1,500 mg with tremelimumab-actl 75 mg every 3 weeks, followed cause immune-mediated thyroid disorders. Thyroiditis can presentreceivingIMJUDOincombinationwithdurvalumab,includingby durvalumab 1,500 mg every 4 weeks (an unapproved regimen withorwithoutendocrinopathy.HypothyroidismcanfollowGrade 4 (0.3%) and Grade 3 (1.5%) adverse reactions. Eventsfor extensive-stage small cell lung cancer). Of these patients, 64% hyperthyroidism. Initiate hormone replacement therapy for hypo- resolved in 6 of the 9 patients. Systemic corticosteroids werereceived the maximum of 5 doses of IMJUDO and 79% received thyroidism or institute medical management of hyperthyroidismrequired in all 9 patients and of these, 7 patients required high-doseat least 4 doses.asclinicallyindicated.WithholdordiscontinueIMJUDOincorticosteroid treatment (at least 40 mg prednisone or equivalentIn this pooled safety population, the most common ( 20%) adverse combination with durvalumab based on the severity [see Dosageper day). reactionswerenausea(37%),decreasedappetite(25%),and and Administration (2.2) in the full Prescribing Information]. Other Immune-Mediated Adverse Reactions fatigue (22%). In this pooled safety population, the most common Thyroiditis: Thefollowingclinicallysignificant,immune-mediatedadverseGrade 3 or 4 ( 10%) laboratory abnormalities were neutropenia IMJUDO with Durvalumab reactions occurred at an incidence of less than 1% each in patients(39%),leukopenia(21%),lymphocytopenia(20%),anemia Immune-mediatedthyroiditisoccurredin1.5%(6/388)ofwho received IMJUDO in combination with durvalumab or were(20%),hyponatremia(14%),lipaseincreased(12%),and patients receiving IMJUDO in combination with durvalumab. Eventsreported with the use of other immune-checkpoint inhibitors. thrombocytopenia (11%).resolved in 2 of the 6 patients. Systemic corticosteroids wereCardiac/vascular: Myocarditis, pericarditis, vasculitis. The data described in this section reflect exposure to IMJUDO in required in 2 patients (2/6) with immune-mediated thyroiditis;Nervoussystem:Meningitis,encephalitis,myelitisandpatients with uHCC included in the HIMALAYA study and in patients of these, 1 patient required high-dose corticosteroid treatmentdemyelination,myasthenicsyndrome/myastheniagraviswith metastatic NSCLC enrolled in the POSEIDON study.(at least 40 mg prednisone or equivalent per day). All patients(including exacerbation), Guillain-Barr syndrome, nerve paresis,Hepatocellular Carcinomarequired other therapy including hormone replacement therapy,autoimmune neuropathy. Unresectable HCC - HIMALAYAthiamazole,carbimazole,propylthiouracil,perchlorate,calciumOcular:Uveitis,iritis,andotherocularinflammatorytoxicitiesThe safety of IMJUDO administered in combination with durvalumab channel blocker, or beta-blocker. can occur. Some cases can be associated with retinal detachment.was evaluated in a total of 388 patients with uHCC in HIMALAYA, Hyperthyroidism:Various grades of visual impairment to include blindness can occur.a randomized, open-label, multicenter study [see Clinical Studies IMJUDO with Durvalumab Ifuveitisoccursincombinationwithotherimmune-mediated(14.1)inthefullPrescribingInformation].Patientsreceived Immune-mediatedhyperthyroidismoccurredin4.6%(18/388)adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome,IMJUDO 300 mg administered as a single intravenous infusion in of patients receiving IMJUDO in combination with durvalumab,as this may require treatment with systemic steroids to reduce thecombination with durvalumab 1,500 mg on the same day, followed includingGrade3(0.3%)adversereactions.Eventsresolvedrisk of permanent vision loss. by durvalumab every 4 weeks or sorafenib 400 mg given orally in 15 of the 18 patients. Two patients (2/18) required high-doseGastrointestinal: Gastritis, duodenitis. twice daily.corticosteroid treatment (at least 40 mg prednisone or equivalentMusculoskeletalandconnectivetissuedisorders:Myositis/Serious adverse reactions occurred in 41% of patients who received per day). Seventeen patients required other therapy (thiamazole,polymyositis, rhabdomyolysis and associated sequelae includingIMJUDOincombinationwithdurvalumab.Seriousadverse carbimazole, propylthiouracil, perchlorate, calcium channel blocker,renal failure, arthritis, polymyalgia rheumatica. reactions in 1% of patients included hemorrhage (6%), diarrhea or beta-blocker). Endocrine: Hypoparathyroidism. (4%), sepsis (2.1%), pneumonia (2.1%), rash (1.5%), vomiting Hypothyroidism: Other (hematologic/immune): Hemolytic anemia, aplastic anemia,(1.3%), acute kidney injury (1.3%), and anemia (1.3%). Fatal IMJUDO with Durvalumab hemophagocyticlymphohistiocytosis,systemicinflammatoryadverse reactions occurred in 8% of patients who received IMJUDO Immune-mediatedhypothyroidismoccurredin11%(42/388)response syndrome, histiocytic necrotizing lymphadenitis (Kikuchiin combination with durvalumab, including death (1%), hemorrhage of patients receiving IMJUDO in combination with durvalumab.lymphadenitis), sarcoidosis, and immune thrombocytopenia. intracranial (0.5%), cardiac arrest (0.5%), pneumonitis (0.5%), US-76417_US-77669_US-77951 Imfinzi-Imjudo US Medicine - The Compendium.indd 8 12/6/23 3:45 PM'