b'IMPORTANT SAFETY INFORMATION (continued)Other Immune-Mediated Adverse Reactions (continued)Immune-Mediated ColitisEndocrine: Hypoparathyroidism.IMFINZI in combination with IMJUDO can cause immune-mediated colitis that is frequently associated with diarrhea. Other (hematologic/immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune- response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternativetransplant rejection.etiologies. Immune-mediated colitis or diarrhea occurred in 6% (23/388) of patients receiving IMFINZI and IMJUDO,Infusion-Related Reactionsincluding Grade 3 (3.6%) adverse reactions. Intestinal perforation has been observed in other studies of IMFINZIIMFINZI and IMJUDO can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related and IMJUDO. reactions. Interrupt, slow the rate of, or permanently discontinue IMFINZI and IMJUDO based on the severity. See USPI Dosing and Immune-Mediated Hepatitis Administration for specific details. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses. IMFINZI in combination with IMJUDO can cause immune-mediated hepatitis, which may be fatal. Immune-mediatedInfusion-related reactions occurred in 10 (2.6%) patients receiving IMFINZI and IMJUDO.hepatitis occurred in 7.5% (29/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.8%), Grade 4 (0.3%) andComplications of Allogeneic HSCT after IMFINZIGrade 3 (4.1%) adverse reactions. Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before Immune-Mediated Endocrinopathies or after being treated with a PD-1/L-1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host-diseaseAdrenal Insufficiency: IMFINZI in combination with IMJUDO can cause primary or secondary adrenal insufficiency. For Grade 2(GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated.febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/L-1 Immune-mediated adrenal insufficiency occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO, includingblockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider Grade 3 (0.3%) adverse reactions. the benefit versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT. Hypophysiti:s IMFINZI in combination with IMJUDO can cause immune-mediated hypophysitis. Hypophysitis can present withEmbryo-Fetal Toxicityacute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can causeBased on its mechanism of action and data from animal studies, IMFINZI and IMJUDO can cause fetal harm when administered hypopituitarism. Initiate symptomatic treatment including hormone replacement as clinically indicated. Immune-mediatedto a pregnant woman. Advise pregnant women of the potential risk to a fetus. In females of reproductive potential, verify hypophysitis/hypopituitarism occurred in 1% (4/388) of patients receiving IMFINZI and IMJUDO. pregnancy status prior to initiating IMFINZI and IMJUDO and advise them to use effective contraception during treatment withThyroid Disorders (Thyroiditis, Hyperthyroidism, and Hypothyroidism): IMFINZI in combination with IMJUDO can cause immune- IMFINZI and IMJUDO and for 3 months after the last dose of IMFINZI and IMJUDO.mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism.LactationInitiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. There is no information regarding the presence of either IMFINZI or IMJUDO in human milk; however, because of the potential forImmune-mediated thyroiditis occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO. serious adverse reactions in breastfed infants from IMFINZI and IMJUDO, advise women not to breastfeed during treatment and for 3Immune-mediated hyperthyroidism occurred in 4.6% (18/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%)months after the last dose.adverse reactions. Adverse Reactions Immune-mediated hypothyroidism occurred in 11% (42/388) of patients receiving IMFINZI and IMJUDO.In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO (n=388), the most common adverseType 1 Diabetes Mellitus, which can present with diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs andreactions (occurring in 20% of patients) were rash (32%), diarrhea (27%), fatigue (26%), pruritus (23%), musculoskeletal pain (22%), symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Two patients 0.5% (2/388) had events of hyperglycemiaand abdominal pain (20%).requiring insulin therapy that had not resolved at last follow-up. In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO (n=388), serious adverse Immune-Mediated Nephritis with Renal Dysfunction reactions occurred in 41% of patients. Serious adverse reactions in 1% of patients included hemorrhage (6%), diarrhea (4%), sepsis (2.1%), pneumonia (2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury (1.3%), and anemia (1.3%). Fatal adverse IMFINZI in combination with IMJUDO can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 1% (4/388) ofreactions occurred in 8% of patients who received IMJUDO in combination with durvalumab, including death (1%), patients receiving IMFINZI and IMJUDO, including Grade 3 (0.5%) adverse reactions. hemorrhage intracranial (0.5%), cardiac arrest (0.5%), pneumonitis (0.5%), hepatic failure (0.5%), and immune-mediated Immune-Mediated Dermatology Reactions hepatitis (0.5%). Permanent discontinuation of treatment regimen due to an adverse reaction occurred in 14% of patients.IMFINZI in combination with IMJUDO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens- The safety and effectiveness of IMFINZI and IMJUDO have not been established in pediatric patients.Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), hasPlease see additional Important Safety Information throughout and Brief Summary of Full Prescribing Information for occurred with PD-1/L-1 and CTLA-4 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treatIMFINZI and IMJUDO on adjacent pages. mild to moderate non-exfoliative rashes. Immune-mediated rash or dermatitis occurred in 4.9% (19/388) of patients receivingYou are encouraged to report the negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions. call 1-800-FDA-1088.Immune-Mediated PancreatitisIMFINZI in combination with IMJUDO can cause immune-mediated pancreatitis. Immune-mediated pancreatitis occurred in 2.3% (9/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions. References: 1.IMFINZI (durvalumab) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2023. 2. IMJUDO (tremelimumab-actl) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2023. 3. Abou-Alfa GK, Lau G, Other Immune-Mediated Adverse Reactions Kudo M, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. NEJM Evid. 2022;1(8). doi:10.1056/The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in patients whoEVIDoa2100070. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hepatocellular Carcinoma V.1.2023. National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed March 13, received IMFINZI in combination with IMJUDO or were reported with the use of other immune-checkpoint inhibitors. 2023. To view the most recent and complete version of the guideline, go online to NCCN.org. 5. Sangro B, Chan SL, Kelley RK, et al.Cardiac/vascular: Myocarditis, pericarditis, vasculitis. Four-year overall survival update from the phase 3 HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. Presented at: 25th ESMO World Congress on Gastrointestinal Cancer; June 28-July 1, 2023; Barcelona, Spain.Nervous system: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including6. Oncology (cancer)/hematologic malignancies approval notifications. US Food and Drug Administration. Updated August 2, 2023. exacerbation), Guillain-Barr syndrome, nerve paresis, autoimmune neuropathy. Accessed August 3, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications 7. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma.Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. VariousN Engl J Med. 2008;359(4):378-390. 8. Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adversewith unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163-1173. 9. Cheng AL, reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk ofQin S, Ikeda M, et al. Updated efficacy and safety data from IMbrave150: atezolizumab plus bevacizumab vs sorafenib for permanent vision loss. unresectable hepatocellular carcinoma. J Hepatol. 2022;76(4):862-873. Gastrointestinal: Gastritis, duodenitis.Musculoskeletal and connective tissue disorder: sMyositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic.IMFINZI and IMJUDO are registered trademarks of the AstraZeneca group of companies. 2023 AstraZeneca. All rights reserved. US-76417 7/23US-76417_US-77669_US-77951 Imfinzi-Imjudo US Medicine - The Compendium.indd 2 12/6/23 3:45 PM'