Imfinzi Full Prescribing Information

1 US-56097 HIGHLIGHTS OF Prescribing INFORMATIONT hese highlights do not include all the Information needed to use Imfinzi safely and effectively. See full Prescribing Information for (durvalumab) injection, for intravenous use Initial Approval: 2017--------------------------------- RECENT MAJOR CHANGES--------------------------------- Indications and Usage, Urothelial Carcinoma Accelerated ApprovalIndication Removed (1) 02/2021 Dosage and Administration ( ) 02/2021 Dosage and Administration, Dosage Modifications ( ) 11/2020 Dosage and Administration ( ) 07/2021 Warnings and Precautions ( , ) 11/2020 Warnings and Precautions ( ) 07/2021--------------------------------- INDICATIONS AND USAGE --------------------------------- Imfinzi is a programmed death-ligand 1 (PD-L1) blocking antibody indicated.

2 For the treatment of adult patients with unresectable, Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. ( ) in combination with etoposide and either carboplatin or cisplatin, as first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). ( )----------------------------- DOSAGE AND ADMINISTRATION ------------------------------ Administer Imfinzi as an intravenous infusion over 60 minutes. ( ) Stage III NSCLC: weight 30 kg and more: 10 mg/kg every 2 weeks or 1500 mg every 4 weeks ( ) weight less than 30 kg: 10 mg/kg every 2 weeks ( ) ES-SCLC: weight 30 kg and more: With etoposide and either carboplatin or cisplatin, administer Imfinzi 1500 mg every 3 weeks in combination with chemotherapy, and then 1500 mg every 4 weeks as a single agent ( ) weight less than 30 kg: With etoposide and either carboplatin or cisplatin, administer Imfinzi 20 mg/kg every 3 weeks in combination with chemotherapy, and then 10 mg/kg every 2 weeks as a single agent ( )---------------------------- DOSAGE FORMS AND STRENGTHS ---------------------------- Injection.

3 500 mg/10 mL (50 mg/mL) solution in a single-dose vial. (3) Injection: 120 mL (50 mg/mL) solution in a single-dose vial. (3)------------------------------------ CONTRAINDICATIONS -----------------------------------None. (4)----------------------------- WARNINGS AND PRECAUTIONS ------------------------------ Immune-Mediated Adverse Reactions ( ) Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune- mediated endocrinopathies, immune-mediated dermatologic adverse reactions, immune-mediated nephritis and renal dysfunction, and solid organ transplant rejection.

4 Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. Withhold or permanently discontinue based on severity and type of reaction. Infusion-Related Reactions: Interrupt, slow the rate of infusion, or permanently discontinue Imfinzi based on the severity of the reaction. ( ) Complications of Allogeneic HSCT: Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD-1/PD-L1 blocking antibody. ( ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception.

5 ( , , )------------------------------------ ADVERSE REACTIONS ----------------------------------- Most common adverse reactions ( 20% of patients with unresectable, Stage III NSCLC) were cough, fatigue, pneumonitis/radiation pneumonitis, upper respiratory tract infections, dyspnea, and rash. ( ) Most common adverse reactions ( 20% of patients with extensive-stage SCLC) were, nausea, fatigue/asthenia, alopecia. ( )To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or USE IN SPECIFIC POPULATIONS -----------------------------Lactation: Advise not to breastfeed. ( )See 17 for PATIENT COUNSELING Information and Medication : 07/2021 FULL Prescribing Information .

6 CONTENTS*1 INDICATIONS AND USAGE Non-Small Cell Lung Cancer Small Cell Lung Cancer2 DOSAGE AND ADMINISTRATION Recommended Dosage Dosage Modifications for Adverse Reactions Preparation and Administration3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS Immune-Mediated Adverse Reactions Infusion-Related Reactions Complications of Allogeneic HSCT after Imfinzi Embryo-Fetal Toxicity6 ADVERSE REACTIONS Clinical Trials Experience Immunogenicity8 USE IN SPECIFIC POPULATIONS Pregnancy Lactation Females and Males of Reproductive Potential Pediatric Use Geriatric Use11 DESCRIPTION12 CLINICAL PHARMACOLOGY Mechanism of Action Pharmacodynamics Pharmacokinetics13 NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility Animal Toxicology and/or Pharmacology14 CLINICAL STUDIES Non-Small Cell Lung Cancer (NSCLC) Small Cell Lung Cancer (SCLC)16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING Information *Sections or subsections omitted from the full Prescribing Information are not (durvalumab) injection, for intravenous use2 FULL Prescribing INFORMATION1 INDICATIONS AND Non-Small Cell Lung CancerIMFINZI is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC)

7 Whose disease has not progressed following concurrent platinum-based chemotherapy and radiation Small Cell Lung CancerIMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).2 DOSAGE AND Recommended DosageThe recommended dosages for Imfinzi as a single agent and Imfinzi in combination with chemotherapy are presented in Table 1 [see Clinical Studies (14)]. Imfinzi is administered as an intravenous infusion over 60 1. Recommended Dosages of IMFINZII ndicationRecommended Imfinzi dosageDuration of TherapyUnresectable stage III NSCLCP atients with a body weight of30 kg and more:10 mg/kg every 2 weeksor1500 mg every 4 weeksPatients with a body weight ofless than 30 kg:10 mg/kg every 2 weeksUntil disease progression,unacceptable toxicity, or amaximum of 12 monthsES-SCLCP atients with a body weight of30 kg and more:1500 mg in combination withchemotherapy1 every 3 weeks(21 days) for 4 cycles,followed by 1500 mg every 4 weeks as a single agentPatients with a body weight ofless than 30 kg.

8 20 mg/kg in combination withchemotherapy1 every 3 weeks(21 days) for 4 cycles,followed by 10 mg/kg every 2 weeks as a single agentUntil disease progression or unacceptable toxicity1 Administer Imfinzi prior to chemotherapy on the same day. When Imfinzi is administered in combination with chemotherapy, refer to the Prescribing Information for etoposide and carboplatin or cisplatin for dosing Dosage Modifications for Adverse ReactionsNo dose reduction for Imfinzi is recommended. In general, withhold Imfinzi for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue Imfinzi for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks of initiating modifications for Imfinzi for adverse reactions that require management different from these general guidelines are summarized in Table 2.

9 Recommended Dosage Modifications for Adverse ReactionsAdverse ReactionSeverity1 Dosage ModificationImmune-Mediated Adverse Reactions [see Warnings and Precautions ( )]PneumonitisGrade 2 Withhold2 Grade 3 or 4 Permanently discontinueColitisGrade 2 or 3 Withhold2 Grade 4 Permanently discontinueAdverse ReactionSeverity1 Dosage ModificationHepatitis with no tumor involvement of the liverALT or AST increases to more than 3 and up to 8 times the ULNortotal bilirubin increases to more than and up to 3 times ULNW ithhold2 ALT or AST increases to more than 8 times ULNor total bilirubin increases to more than 3 times the ULNP ermanently discontinueHepatitis with tumor involvement of the liver3 AST or ALT is more than 1 and up to 3 times ULN at baseline and increases to more than 5 and up to 10 times ULNorAST or ALT is more than 3 and up to 5 times ULN at baseline and increases to more than 8 and up to

10 10 times ULNW ithhold2 AST or ALT increases to more than 10 times ULN orTotal bilirubin increases to more than 3 times ULNP ermanently discontinueEndocrinopathiesGrade 3 or 4 Withhold until clinically stable or permanently discontinue depending on severityNephritis with RenalDysfunctionGrade 2 or 3increased blood creatinineWithhold2 Grade 4 increasedblood creatininePermanently discontinueExfoliative DermatologicConditionsSuspected SJS, TEN, or DRESSW ithhold2 Confirmed SJS, TEN, or DRESSP ermanently discontinueMyocarditisGrade 2, 3, or 4 Permanently discontinueNeurological ToxicitiesGrade 2 Withhold2 Grade 3 or 4 Permanently discontinueOther Adverse ReactionsInfusion-related reactions [see Warnings and Precautions ( )]Grade 1 or 2 Interrupt or slow the rate of infusionGrade 3 or 4 Permanently discontinueALT = alanine aminotransferase, AST = aspartate aminotransferase, DRESS = Drug Rash with Eosinophilia and Systemic Symptoms, SJS = Stevens Johnson Syndrome, TEN = toxic epidermal necrolysis, ULN = upper limit normal1 Based on National Cancer Institute Common Terminology Criteria for Adverse Events, version Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper.