10 ML durvalumab 50 MG/ML Injection [Imfinzi]

INDICATIONS AND USAGE IMFINZI is a programmed death-ligand 1 (PD-L1) blocking antibody indicated: • in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by IMFINZI continued as a single agent as adjuvant treatment after surgery, for the treatment of adult patients with resectable (tumors ≥ 4 cm and/or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements. ( 1.1 ) • as a single agent, for the treatment of adult patients with unresectable, Stage III NSCLC whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. ( 1.1 ) • in combination with tremelimumab-actl and platinum-based chemotherapy, for the treatment of adult patients with metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations. ( 1.1 ) • as a single agent, for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy. ( 1.2 ) • 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). ( 1.2 ) • in combination with gemcitabine and cisplatin, as treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC). ( 1.3 ) • in combination with tremelimumab-actl, for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC). ( 1.4 ) • in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent, for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) as determined by an FDA-approved test. ( 1.5 , 2.1 ) • in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by single agent IMFINZI as adjuvant treatment following radical cystectomy, for the treatment of adult patients with muscle invasive bladder cancer (MIBC). ( 1.6 ) • in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy as neoadjuvant and adjuvant treatment, followed by single agent IMFINZI, for the treatment of adult patients with resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC). ( 1.7 ) 1.1 Non-Small Cell Lung Cancer • IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by IMFINZI continued as a single agent as adjuvant treatment after surgery, is indicated for the treatment of adult patients with resectable (tumors ≥ 4 cm and/or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements. • IMFINZI, as a single agent, is indicated for the treatment of adult patients with unresectable Stage III NSCLC whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT). • IMFINZI, in combination with tremelimumab-actl and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations. 1.2 Small Cell Lung Cancer • IMFINZI, as a single agent, is indicated for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT). • IMFINZI, 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). 1.3 Biliary Tract Cancers IMFINZI, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC). 1.4 Hepatocellular Carcinoma IMFINZI, in combination with tremelimumab-actl, is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC). 1.5 Endometrial Cancer IMFINZI, in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent, is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) as determined by an FDA-approved test [see Dosage and Administration (2.1)]. 1.6 Bladder Cancer IMFINZI in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by single agent IMFINZI as adjuvant treatment following radical cystectomy, is indicated for the treatment of adult patients with muscle invasive bladder cancer (MIBC). 1.7 Gastric or gastroesophageal junction adenocarcinoma IMFINZI in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) as neoadjuvant and adjuvant treatment, followed by single-agent IMFINZI, is indicated for the treatment of adult patients with resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC).

DOSAGE AND ADMINISTRATION • Administer IMFINZI as an intravenous infusion over 60 minutes after dilution. ( 2.4 ) • Neoadjuvant and Adjuvant Treatment of Resectable NSCLC: ∘ Weight ≥ 30 kg: Neoadjuvant : IMFINZI 1,500 mg in combination with chemotherapy every 3 weeks for up to 4 cycles prior to surgery. Adjuvant : IMFINZI 1,500 mg as a single agent every 4 weeks for up to 12 cycles after surgery. ( 2.2 ) ∘ Weight < 30 kg Neoadjuvant : IMFINZI 20 mg/kg every 3 weeks in combination with chemotherapy for up to 4 cycles prior to surgery. Adjuvant : 20 mg/kg every 4 weeks as a single agent for up to 12 cycles after surgery. ( 2.2 ) • Unresectable Stage III NSCLC, following concurrent platinum-based chemotherapy and radiation therapy: ∘ Weight ≥ 30 kg: IMFINZI 10 mg/kg every 2 weeks or 1,500 mg every 4 weeks. ( 2.2 ) ∘ Weight < 30 kg: IMFINZI 10 mg/kg every 2 weeks. ( 2.2 ) • Metastatic NSCLC: ∘ Weight ≥ 30 kg: IMFINZI 1,500 mg every 3 weeks in combination with tremelimumab-actl 75 mg and platinum-based chemotherapy for 4 cycles, and then administer IMFINZI 1,500 mg every 4 weeks as a single agent with histology-based pemetrexed maintenance therapy every 4 weeks, and a fifth dose of tremelimumab-actl 75 mg in combination with IMFINZI dose 6 at week 16. ( 2.2 ) ∘ Weight < 30 kg: IMFINZI 20 mg/kg every 3 weeks in combination with tremelimumab-actl 1 mg/kg and platinum-based chemotherapy, and then administer IMFINZI 20 mg/kg every 4 weeks as a single agent with histology-based pemetrexed therapy every 4 weeks, and a fifth dose of tremelimumab-actl 1 mg/kg in combination with IMFINZI dose 6 at week 16. ( 2.2 ) • LS-SCLC, following concurrent platinum-based chemotherapy and radiation therapy: ∘ Weight ≥ 30 kg: 1,500 mg every 4 weeks. ( 2.2 ) ∘ Weight < 30 kg: 20 mg/kg every 4 weeks. ( 2.2 ) • ES-SCLC: ∘ Weight ≥ 30 kg: With etoposide and either carboplatin or cisplatin, administer IMFINZI 1,500 mg every 3 weeks in combination with chemotherapy, and then 1,500 mg every 4 weeks as a single agent. ( 2.2 ) ∘ Weight < 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. ( 2.2 ) • BTC: ∘ Weight ≥ 30 kg: administer IMFINZI 1,500 mg every 3 weeks in combination with chemotherapy, and then 1,500 mg every 4 weeks as a single agent. ( 2.2 ) ∘ Weight < 30 kg: administer IMFINZI 20 mg/kg every 3 weeks in combination with chemotherapy, and then 20 mg/kg every 4 weeks as a single agent. ( 2.2 ) • uHCC: ∘ Weight ≥ 30 kg: IMFINZI 1,500 mg in combination with tremelimumab-actl 300 mg as a single dose at Cycle 1/Day 1, followed by IMFINZI as a single agent every 4 weeks. ( 2.2 ) ∘ Weight < 30 kg: IMFINZI 20 mg/kg in combination with tremelimumab-actl 4 mg/kg as a single dose at Cycle 1/Day 1, followed by IMFINZI as a single agent every 4 weeks. ( 2.2 ) • dMMR endometrial cancer: ∘ Weight ≥ 30 kg: IMFINZI 1,120 mg in combination with carboplatin and paclitaxel every 3 weeks for 6 cycles, followed by IMFINZI 1,500 mg every 4 weeks as a single agent. ( 2.1 , 2.2 ) ∘ Weight < 30 kg: IMFINZI 15 mg/kg in combination with carboplatin and paclitaxel every 3 weeks for 6 cycles, followed by IMFINZI 20 mg/kg every 4 weeks as a single agent. ( 2.1 , 2.2 ) • MIBC: ∘ Weight ≥ 30 kg: Neoadjuvant: IMFINZI 1,500 mg in combination with gemcitabine and cisplatin every 3 weeks for 4 cycles prior to surgery. Adjuvant: IMFINZI 1,500 mg every 4 weeks as a single agent for up to 8 cycles after surgery. ( 2.2 ) ∘ Weight < 30 kg: Neoadjuvant: IMFINZI 20 mg/kg in combination with gemcitabine and cisplatin every 3 weeks for 4 cycles prior to surgery. Adjuvant: IMFINZI 20 mg/kg every 4 weeks as a single agent for up to 8 cycles after surgery. ( 2.2 ) • See full Prescribing Information for preparation and administration instructions and dosage modifications for adverse reactions. 2.1 Patient Selection Advanced or Recurrent dMMR Endometrial Cancer Select patients for treatment based on the presence of dMMR in tumor specimens [see Clinical Studies (14.5) ]. Information on FDA-approved tests for the detection of dMMR status in endometrial cancer is available at https://www.fda.gov/companiondiagnostics . 2.2 Recommended Dosage The recommended dosages for IMFINZI as a single agent and IMFINZI in combination with other therapeutic agents are presented in Table 1. The recommended dosage schedule and regimens for IMFINZI for the treatment of metastatic NSCLC are provided in Tables 2 and 3 [see Indications and Usage (1.1) ]. Administer IMFINZI as a 60 minute intravenous infusion after dilution [ see Dosage and Administration (2.3) ]. Table 1. Recommended Dosages of IMFINZI Indication Recommended IMFINZI Dosage Duration of Therapy Neoadjuvant and Adjuvant Treatment of Resectable NSCLC Patients with a body weight of ≥ 30 kg: Neoadjuvant: IMFINZI 1,500 mg in combination with chemotherapy Administer IMFINZI prior to chemotherapy on the same day. Refer to the Prescribing Information for the agent administered in combination with IMFINZI for recommended dosage information, as appropriate. every 3 weeks for up to 4 cycles prior to surgery Adjuvant: IMFINZI 1,500 mg as a single agent every 4 weeks for up to 12 cycles after surgery. Patients with a body weight of < 30 kg: Neoadjuvant: IMFINZI 20 mg/kg every 3 weeks in combination with chemotherapy for up to 4 cycles prior to surgery. Adjuvant: IMFINZI 20 mg/kg every 4 weeks for up to 12 cycles as a single agent after surgery. Until disease progression that precludes definitive surgery, recurrence, unacceptable toxicity, or a maximum of 12 cycles after surgery Unresectable Stage III NSCLC Following concurrent platinum-based chemotherapy and radiation therapy: Patients with a body weight of ≥ 30 kg: 10 mg/kg every 2 weeks or 1,500 mg every 4 weeks Patients with a body weight of < 30 kg: 10 mg/kg every 2 weeks Until disease progression, unacceptable toxicity, or a maximum of 12 months Limited Stage SCLC Following concurrent platinum-based chemotherapy and radiation therapy: Patients with a body weight of ≥ 30 kg: 1,500 mg every 4 weeks Patients with a body weight of < 30 kg: 20 mg/kg every 4 weeks Until disease progression, unacceptable toxicity, or a maximum of 24 months Extensive Stage SCLC Patients with a body weight of ≥ 30 kg: 1,500 mg in combination with chemotherapy every 3 weeks (21 days) for 4 cycles, followed by 1,500 mg every 4 weeks as a single agent Patients with a body weight of < 30 kg: 20 mg/kg in combination with chemotherapy every 3 weeks (21 days) for 4 cycles, followed by 10 mg/kg every 2 weeks as a single agent Until disease progression or until unacceptable toxicity BTC Patients with a body weight of ≥ 30 kg: 1,500 mg in combination with chemotherapy every 3 weeks (21 days) up to 8 cycles followed by 1,500 mg every 4 weeks as a single agent Patients with a body weight of < 30 kg: 20 mg/kg in combination with chemotherapy every 3 weeks (21 days) up to 8 cycles, followed by 20 mg/kg every 4 weeks as a single agent Until disease progression or until unacceptable toxicity uHCC Patients with a body weight of ≥ 30 kg: IMFINZI 1,500 mg following a single dose of tremelimumab-actl Administer tremelimumab-actl prior to IMFINZI on the same day. When tremelimumab-actl is administered in combination with IMFINZI, refer to the Prescribing Information for tremelimumab-actl dosing information. 300 mg at Day 1 of Cycle 1; Continue IMFINZI 1,500 mg as a single agent every 4 weeks Patients with a body weight of < 30 kg: IMFINZI 20 mg/kg following a single dose of tremelimumab-actl 4 mg/kg at Day 1 of Cycle 1; Continue IMFINZI 20 mg/kg as a single agent every 4 weeks After Cycle 1 of combination therapy, administer IMFINZI as a single agent every 4 weeks until disease progression or unacceptable toxicity dMMR endometrial cancer Patients with a body weight of ≥ 30 kg: IMFINZI 1,120 mg in combination with carboplatin and paclitaxel every 3 weeks

WARNINGS AND PRECAUTIONS • Immune-Mediated Adverse Reactions ( 5.1 ) ∘ 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, solid organ transplant rejection, and immune-mediated pancreatitis. o Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. o 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. ( 5.2 ) • 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. (5.3) • Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception. ( 5.4 , 8.1 , 8.3 ) 5.1 Immune-Mediated Adverse Reactions IMFINZI is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death-receptor 1 (PD-1) or the PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. The incidence and severity of immune-mediated adverse reactions were similar when IMFINZI was administered as a single agent or in combination with chemotherapy or in combination with tremelimumab-actl and platinum-based chemotherapy, unless otherwise noted. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment with a PD 1/PD L1 blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue IMFINZI depending on severity [see Dosage and Administration (2.3) ] . In general, if IMFINZI requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below. Immune-Mediated Pneumonitis IMFINZI can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. IMFINZI as a Single Agent In Patients Who Did Not Receive Recent Prior Radiation In patients who received IMFINZI on clinical studies in which radiation therapy was generally not administered immediately prior to initiation of IMFINZI, the incidence of immune-mediated pneumonitis was 2.4% (34/1414), including fatal (< 0.1%), and Grade 3-4 (0.4%) adverse reactions. Events resolved in 19 of the 34 patients and resulted in permanent discontinuation in 5 patients. Systemic corticosteroids were required in 19 patients (19/34) with pneumonitis who did not receive chemoradiation prior to initiation of IMFINZI. The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to IMFINZI were similar whether IMFINZI was given as a single agent in patients with various cancers in a pooled data set or in patients with ES-SCLC or BTC when given in combination with chemotherapy. In Patients Who Received Recent Prior Radiation The incidence of pneumonitis (including radiation pneumonitis) in patients with unresectable Stage III NSCLC following definitive chemoradiation within 42 days prior to initiation of IMFINZI in PACIFIC was 18.3% (87/475) in patients receiving IMFINZI and 12.8% (30/234) in patients receiving placebo. Of the patients who received IMFINZI (475), 1.1% had a fatal adverse reaction and 2.7% had Grade 3 adverse reactions. Events resolved in 50 of the 87 (57%) patients and resulted in permanent discontinuation in 27 of the 87 (31%) patients. Systemic corticosteroids were required in 64 patients (64/87) with pneumonitis who had received chemoradiation prior to initiation of IMFINZI, while 2 patients required use of infliximab with high-dose steroids. The incidence of pneumonitis (including radiation pneumonitis) in patients with LS-SCLC following chemoradiation within 42 days prior to initiation of IMFINZI in ADRIATIC was 14% (37/262) in patients receiving IMFINZI and 6% (16/265) in patients receiving placebo. Of the patients who received IMFINZI (262), 0.4% had a fatal adverse reaction and 2.7% had Grade 3 adverse reactions. Events resolved in 19 of the 37 (51%) patients and resulted in permanent discontinuation in 18 of the 37 (49%) patients. Systemic corticosteroids were required in all patients, while 1 patient required use of infliximab with high-dose steroids . IMFINZI with Tremelimumab-actl Immune-mediated pneumonitis occurred in 1.3% (5/388) of patients receiving IMFINZI in combination with tremelimumab-actl, including fatal (0.3%) and Grade 3 (0.2%) adverse reactions. Events resolved in 3 of the 5 patients and resulted in permanent discontinuation in 1 patient. Systemic corticosteroids were required in all patients; of these, 4 patients required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). One patient (1/5) required other immunosuppressants. IMFINZI with Tremelimumab-actl and Platinum-Based Chemotherapy Immune-mediated pneumonitis occurred in 3.5% (21/596) of patients receiving IMFINZI in combination with tremelimumab-actl and platinum-based chemotherapy, including fatal (0.5%), and Grade 3 (1%) adverse reactions. Events resolved in 11 of the 21 patients and resulted in permanent discontinuation in 7 patients. Systemic corticosteroids were required in all patients with immune-mediated pneumonitis, while 1 patient (1/21) required other immunosuppressants. Immune-Mediated Colitis IMFINZI can cause immune-mediated colitis that is frequently associated with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. IMFINZI as a Single Agent Immune-mediated colitis occurred in 2% (37/1889) of patients receiving IMFINZI, including Grade 4 (< 0.1%) and Grade 3 (0.4%) adverse reactions. Events resolved in 27 of the 37 patients and resulted in p

CONTRAINDICATIONS None. None. ( 4 )

Mechanism of Action Expression of programmed cell death ligand-1 (PD-L1) can be induced by inflammatory signals (e.g., IFN-gamma) and can be expressed on both tumor cells and tumor-associated immune cells in the tumor microenvironment. PD-L1 blocks T-cell function and activation through interaction with PD-1 and CD80 (B7.1). By binding to its receptors, PD-L1 reduces cytotoxic T-cell activity, proliferation, and cytokine production. Durvalumab is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80 (B7.1). Blockade of PD-L1/PD-1 and PD-L1/CD80 interactions releases the inhibition of immune responses, without inducing antibody dependent cell-mediated cytotoxicity (ADCC). PD-L1 blockade with durvalumab led to increased T-cell activation in vitro and decreased tumor size in co-engrafted human tumor and immune cell xenograft mouse models.