b'IMJUDO (tremelimumab-actl) injection, Table4.RecommendedDosageModificationsforAdverseAdministrationfor intravenous useReactions (contd) AdministerIMJUDOinfusionsolutionintravenouslyover Initial U.S. Approval: 2022AdverseDosage60 minutes through an intravenous line containing a sterile, Brief Summary of Prescribing InformationReaction Severity 1 Modification low-protein binding 0.2 or 0.22 micron filter.For complete prescribing information consultAST or ALT is more than Use separate infusion bags and filters for each drug product.official package insert. 1 and up to 3 times ULN IMJUDO In Combination with Other Products INDICATIONS AND USAGE at baseline and increases Administer all drug products as separate intravenous infusions.Hepatocellular Carcinoma to more than 5 and up to Do not co-administer other drugs through the same infusion line.IMJUDO, in combination with durvalumab, is indicated for the10 times ULN Combination Regimens: Order of Infusionstreatmentofadultpatientswithunresectablehepatocellularor Withhold 2 IMJUDO in Combination with Durvalumabcarcinoma (uHCC). HepatitisAST or ALT is more than Infuse IMJUDO, followed by durvalumab on the same day with tumor 3 and up to 5 times ULN of dosing.DOSAGE AND ADMINISTRATION involvement at baseline and increasesRecommended Dosage of the liver 3 to more than 8 and up to Combination Regimens: Infusion InstructionsThe recommended dosages of IMJUDO are presented in Table 1. 10 times ULN IMJUDO in Combination with DurvalumabAdminister IMJUDO as an intravenous infusion after dilution asAST or ALT increases toObserve patient for 60 minutes following completion of IMJUDO recommended [see Dosage and Administration (2.3) in the fullmore than 10 times ULN Permanentlyinfusion[seeWarningsandPrecautions(5.2)inthefull Prescribing Information]. or discontinue Prescribing Information]. Then administer durvalumab as a IMJUDO in Combination with DurvalumabTotal bilirubin increases toseparate intravenous infusion over 60 minutes.Table 1. Recommended dosage of IMJUDO more than 3 times ULN CONTRAINDICATIONSWithholdNone.Indication Recommended IMJUDODuration of Therapy until clinicallyWARNINGS AND PRECAUTIONSDosage stable or Endocrinopathies Grade 3 or 4 permanentlySevere and Fatal Immune-Mediated Adverse ReactionsuHCC Patients with a body weight After Cycle 1 of discontinueIMJUDO is a monoclonal antibody that blocks T-cell inhibitory of 30 kg and more: combination depending onsignalsinducedbytheCTLA-4pathway,therebyremoving A single dose of IMJUDO 1therapy, administerseverity inhibition of the immune response. In combination with durvalumab, 300 mg followed bydurvalumab as a a PD-L1 inhibitor, these drugs have the potential for induction of durvalumab 21,500 mg at single agent every Nephritis Grade 2 or 3 increased Withhold 2 immune-mediated adverse reactions. Immune-mediated adverse Day 1 of Cycle 1; 4 weeks until with Renal blood creatinine reactions listed herein may not be inclusive of all possible severe Continue durvalumab disease progressionDysfunction Grade 4 increased bloodPermanentlyand fatal immune-mediated reactions.1,500 mg as a single agentor unacceptablecreatinine discontinue Immune-mediated adverse reactions, which may be severe or every 4 weeks toxicity Exfoliative Suspected SJS, TEN, orWithhold 2 fatal, can occur in any organ system or tissue. Immune-mediated Patients with a body weightDermatologic DRESS adverse reactions can occur at any time after starting IMJUDO in of less than 30 kg: Conditions Confirmed SJS, TEN, orPermanentlycombination with durvalumab. While immune-mediated adverse A single dose of IMJUDO 1DRESS discontinue reactions usually manifest during treatment, immune-mediated 4 mg/kg followed byPermanentlyadversereactionscanalsomanifestafterdiscontinuationof durvalumab 220 mg/kg at Myocarditis Grade 2, 3, or 4 discontinue IMJUDO and/or durvalumab.Day 1 of Cycle 1; Grade 2 Withhold 2 Earlyidentificationandmanagementofimmune-mediated Continue durvalumab Neurological Permanentlyadverse reactions are essential to ensure safe use of IMJUDO in 20 mg/kg as a single agentToxicities Grade 3 or 4 discontinue combination with durvalumab. Monitor for signs and symptoms every 4 weeks that may be clinical manifestations of underlying immune-mediated Other Adverse Reactions adverse reactions. Evaluate clinical chemistries including liver 1Administer IMJUDO prior to durvalumab on the same day. enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, 2Refer to the Prescribing Information for durvalumab dosing information. Infusion-relatedInterrupt and thyroid function at baseline and before each dose. Institute reactions [seeGrade 1 or 2 or slow medical management promptly, including specialty consultation Dosage Modifications for Adverse Reactions Warnings andthe rate ofas appropriate.No dose reduction for treatment is recommended. In general,Precautions infusionwithholdtreatmentregimenforsevere(Grade3)immune-(5.2) in the full PermanentlyWithholdorpermanentlydiscontinueIMJUDOanddurvalumab mediated adverse reactions. Permanently discontinue treatmentPrescribing Grade 3 or 4 discontinue depending on severity [see Dosage and Administration (2.2) in the regimen for life-threatening (Grade 4) immune-mediated adverseInformation] full Prescribing Information]. In general, if combination of IMJUDO reactions, recurrent severe (Grade 3) immune-mediated reactionsALT=alanineaminotransferase,AST=aspartateaminotransferase,and durvalumab requires interruption or discontinuation, administer thatrequiresystemicimmunosuppressivetreatment,oranDRESS=DrugRashwithEosinophiliaandSystemicSymptoms,systemiccorticosteroidtherapy(1to2mg/kg/dayprednisone inabilitytoreducecorticosteroiddoseto10mgorlessofSJS = Stevens Johnson Syndrome, TEN = toxic epidermal necrolysis,orequivalent)untilimprovementtoGrade1orless.Upon ULN = upper limit normal improvement to Grade 1 or less, initiate corticosteroid taper and prednisone or equivalent per day within 12 weeks of initiating1Based on National Cancer Institute Common Terminology Criteria forcontinue to taper over at least 1 month. Consider administration corticosteroids. Adverse Events, version 4.03.Recommended treatment modifications are presented in Table 4. 2Resume in patients with complete or partial resolution (Grade 0 to 1)ofothersystemicimmunosuppressantsinpatientswhose immune-mediatedadversereactionsarenotcontrolledwith Table4.RecommendedDosageModificationsforAdverseafter corticosteroid taper. Permanently discontinue if no complete or partialcorticosteroid therapy.Reactions resolution within 12 weeks of initiating steroids or an inability to reduce corticosteroid dose to 10 mg of prednisone or less per day (or equivalent)Toxicity management guidelines for adverse reactions that do not within 12 weeks of initiating corticosteroids.AdverseDosage3 necessarily require systemic steroids (e.g., endocrinopathies and Reaction Severity 1 ModificationIf AST and ALT are less than or equal to ULN at baseline in patients withdermatologic reactions) are discussed below.liver involvement, withhold or permanently discontinue durvalumab based Immune-Mediated Adverse Reactions [see Warnings and on recommendations for hepatitis with no liver involvement. Immune-Mediated PneumonitisPrecautions (5.1) in the full Prescribing Information] IMJUDOincombinationwithdurvalumabcancauseimmune- Preparation and Administration mediated pneumonitis, which may be fatal.Grade 2 Withhold 2 Preparation IMJUDO with DurvalumabPneumonitis Grade 3 or 4 PermanentlyVisuallyinspectdrugproductforparticulatematterandImmune-mediated pneumonitis occurred in 1.3% (5/388) of patients discontinue discoloration. Discard if the solution is cloudy, discolored, orreceiving IMJUDO in combination with durvalumab, including fatal Grade 2 Withhold 2 visible particles are observed. (0.3%) and Grade 3 (0.2%) adverse reactions. Events resolved in Do not shake the vial. 3 of the 5 patients and resulted in permanent discontinuation in Colitis Grade 3 or 4 PermanentlyWithdraw the required volume from the vial(s) of IMJUDO and1 patient. Systemic corticosteroids were required in all patients; discontinue discard the vial with any unused portion. of these, 4 patients required high-dose corticosteroid treatment Intestinal PermanentlyTransfer into an intravenous bag containing 0.9% Sodium(at least 40 mg prednisone or equivalent per day). One patient perforation Any grade discontinue Chloride Injection, USP or 5% Dextrose Injection, USP and(1/5) required other immunosuppressants.dilute to a concentration between 0.1 mg/mL and 10 mg/mL.Immune-Mediated ColitisALT or AST increases toMixdilutedsolutionbygentleinversion.DonotshakeIMJUDO in combination with durvalumab and platinum-based more than 3 and up to the solution. chemotherapy can cause immune-mediated colitis, which may be fatal. 8 times the ULN 2 Storage of Diluted IMJUDO Infusion Solutionor Withhold IMJUDO does not contain a preservative. Administer infusionIMJUDOincombinationwithdurvalumabcancauseimmune- Hepatitis with total bilirubin increases tosolution immediately once prepared. If infusion solution is notmediatedcolitisthatisfrequentlyassociatedwithdiarrhea. no tumor more than 1.5 and up to administered immediately and needs to be stored, the totalCytomegalovirus (CMV) infection/reactivation has been reported involvement 3 times ULN time from preparation to the start of administration shouldin patients with corticosteroid-refractory immune-mediated colitis. Incasesofcorticosteroid-refractorycolitis,considerrepeating of the liver ALT or AST increases tonot exceed: infectious workup to exclude alternative etiologies.more than 8 times ULN Permanentlyo24 hours in a refrigerator at 2C to 8C (36F to 46F) IMJUDO with Durvalumabor discontinue o24 hours at room temperature up to 30C (86F) Immune-mediated colitis or diarrhea occurred in 6% (23/388) total bilirubin increases toDo not freeze. of patients receiving IMJUDO in combination with durvalumab, more than 3 times the ULN Do not shake. including Grade 3 (3.6%) adverse reactions. Events resolved in US-76417_US-77669_US-77951 Imfinzi-Imjudo US Medicine - The Compendium.indd 7 12/6/23 3:45 PM'