ASCO Connection

July 2017

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Table 1. Recommended Treatment Modifications for IMFINZI (cont'd) IMFINZI™ (durvalumab) injection, for intravenous use Initial U.S. Approval: 2017 Brief Summary of Prescribing Information. For complete prescribing information consult official package insert. INDICATIONS AND USAGE IMFINZI is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who: % have disease progression during or following platinum-containing chemotherapy. % have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials [see Clinical Studies (14.1) in the full Prescribing Information]. DOSAGE AND ADMINISTRATION Recommended Dosing The recommended dose of IMFINZI is 10 mg/kg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity. Dose Modifications No dose reductions are recommended. Withhold and/or discontinue IMFINZI to manage adverse reactions as described in Table 1. Table 1. Recommended Treatment Modifications for IMFINZI Adverse Reactions Severity a IMFINZI Treatment Modification Corticosteroid Treatment Unless Otherwise Specified Pneumonitis [see Warnings and Precautions (5.1)] Grade 2 Withhold dose b Initial dose of 1 mg/kg/day to 2 mg/kg/day prednisone or equivalent followed by a taper Grade 3 or 4 Permanently discontinue Initial dose of 1 mg/kg/day to 4 mg/kg/day prednisone or equivalent followed by a taper Hepatitis [see Warnings and Precautions (5.2)] Grade 2 ALT or AST >3-5xULN or total bilirubin >1.5-3xULN Withhold dose b Initial dose of 1 mg/kg/day to 2 mg/kg/day prednisone or equivalent followed by a taper Grade 3 ALT or AST ≤8xULN or total bilirubin ≤5xULN Grade 3 ALT or AST >8xULN or total bilirubin >5xULN Permanently discontinue Concurrent ALT or AST >3xULN and total bilirubin >2xULN with no other cause Colitis or diarrhea [see Warnings and Precautions (5.3)] Grade 2 Withhold dose b Initial dose of 1 mg/kg/day to 2 mg/kg/day prednisone or equivalent followed by a taper Grade 3 or 4 Permanently discontinue Hypothyroidism [see Warnings and Precautions (5.4)] Grade 2-4 Initiate thyroid hormone replacement as clinically indicated Hyperthyroidism [see Warnings and Precautions (5.4)] Grade 2-4 Withhold dose until clinically stable Symptomatic management Adrenal insufficiency, Hypophysitis/ Hypopituitarism [see Warnings and Precautions (5.4)] Grade 2-4 Withhold dose until clinically stable Initiate 1 to 2 mg/kg/day prednisone or equivalent followed by a taper and hormone replacement as clinically indicated Type 1 Diabetes Mellitus [see Warnings and Precautions (5.4)] Grade 2-4 Withhold dose until clinically stable Initiate treatment with insulin as clinically indicated Nephritis [see Warnings and Precautions (5.5)] Grade 2 Creatinine >1.5-3x ULN Withhold dose b Initial dose of 1 mg/kg/day to 2 mg/kg/day prednisone or equivalent followed by a taper Grade 3 Creatinine >3-6x ULN Permanently discontinue Grade 4 Creatinine >6x ULN Rash or dermatitis [see Warnings and Precautions (5.5)] Grade 2 for >1 week Withhold dose b Consider initial dose of 1 mg/kg/day to 2 mg/kg/day prednisone or equivalent followed by a taper Grade 3 Grade 4 Permanently discontinue Infection [see Warnings and Precautions (5.6)] Grade 3 or 4 Withhold dose Symptomatic management; treat with anti-infectives for suspected or confirmed infections Infusion-related reactions [see Warnings and Precautions (5.7)] Grade 1 or 2 Interrupt or slow the rate of infusion Consider pre-medications with subsequent doses Grade 3 or 4 Permanently discontinue Adverse Reactions Severity a IMFINZI Treatment Modification Corticosteroid Treatment Unless Otherwise Specified Other Grade 3 Withhold dose b Symptomatic management Grade 4 Permanently discontinue Consider initial dose of 1 mg/kg/day to 4 mg/kg/day prednisone or equivalent followed by taper a Common Terminology Criteria for Adverse Events, version 4.03. ALT: alanine aminotransferase; AST: aspartate aminotransferase; ULN: upper limit of normal. b Based on severity of the adverse reactions, IMFINZI should be withheld and corticosteroids administered. Consider increasing dose of corticosteroids and/or other systemic immunosuppressants if there is worsening or no improvement. Corticosteroid taper should be initiated when adverse reaction improves to < Grade 1 and should be continued over at least 1 month. For adverse reactions that do not result in permanent discontinuation, resume treatment when adverse reaction returns to ≤ Grade 1 and the corticosteroid dose has been reduced to <10 mg prednisone or equivalent per day. Preparation and Administration Preparation % Visually inspect drug product for particulate matter and discoloration. IMFINZI is clear to opalescent, colorless to slightly yellow solution, free from visible particles. Discard the vial if the solution is cloudy, discolored, or visible particles are observed. % Do not shake the vial. % Withdraw the required volume from the vial(s) of IMFINZI and transfer into an intravenous bag containing 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. Mix diluted solution by gentle inversion. Do not shake the solution. The final concentration of the diluted solution should be between 1 mg/mL and 15 mg/mL. % Discard partially used or empty vials of IMFINZI. Storage of Infusion Solution IMFINZI does not contain a preservative. Administer infusion solution immediately once prepared. If infusion solution is not administered immediately and needs to be stored, the total time from vial puncture to the start of the administration should not exceed: % 24 hours in a refrigerator at 2°C to 8°C (36°F to 46°F) % 4 hours at room temperature up to 25°C (77°F) Do not freeze. Do not shake. Administration % Administer infusion solution intravenously over 60 minutes through an intravenous line containing a sterile, low-protein binding 0.2 or 0.22 micron in-line filter. % Do not co-administer other drugs through the same infusion line. DOSAGE FORMS AND STRENGTHS Injection: 120 mg/2.4mL (50 mg/mL) and 500 mg/10mL (50 mg/mL) clear to opalescent, colorless to slightly yellow solution in a single-dose vial. CONTRAINDICATIONS None. WARNINGS AND PRECAUTIONS Immune-Mediated Pneumonitis Immune-mediated pneumonitis or interstitial lung disease occurred in patients receiving IMFINZI. Monitor patients for signs and symptoms of pneumonitis. Evaluate patients with suspected pneumonitis with radiographic imaging and manage with treatment modifications and cortico- steroids [see Dosage and Administration (2.2) in the full Prescribing Information]. In Study 1 (n=182), one patient (0.5%) died from immune-mediated pneumonitis. In the combined safety database (n=1414), of patients treated with IMFINZI 10 mg/kg every 2 weeks, immune- mediated pneumonitis occurred in 32 (2.3%) patients including fatal pneumonitis in one (0.1%) patient and Grade 3-4 in six (0.4%) patients. The median time to onset was 55.5 days (range: 24-423 days). Seventeen (1.2%) patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). IMFINZI was interrupted in 12 patients and discontinued in five (0.4%) patients. Resolution occurred in 18 (1.3%) patients. Immune-Mediated Hepatitis Immune-mediated hepatitis occurred in patients receiving IMFINZI. Monitor patients for abnormal liver tests each cycle during treatment with IMFINZI. Manage immune-mediated hepatitis with treatment modifications and corticosteroids [see Dosage and Administration (2.2) in the full Prescribing Information]. In Study 1, one (0.5%) patient died from immune-mediated hepatitis. An additional two (1.1%) patients experienced immune-mediated hepatitis, including Grade 3 in one (0.5%) patient. In the combined safety database, immune-mediated hepatitis occurred in 16 (1.1%) patients including fatal hepatitis in one (<0.1%) patient and Grade 3 in nine (0.6%) patients. The median time to onset was 51.5 days (range: 15-312 days). Twelve (0.8%) of the 16 patients received high-dose cortico- steroid treatment. One patient also received mycophenolate treatment. IMFINZI was interrupted in five (0.3%) patients and discontinued in three (0.2%) patients. Resolution occurred in nine (0.6%) patients. In the combined safety database, Grade 3 or 4 elevations in ALT occurred in 40/1342 (3.0%) of patients, AST in 58/1336 (4.3%), and total bilirubin in 37/1341 (2.8%) of patients. Immune-Mediated Colitis Immune-mediated colitis or diarrhea occurred in patients receiving IMFINZI. Monitor patients for signs and symptoms of colitis or diarrhea and manage with treatment modifications, anti-diarrheal agents, and corticosteroids [see Dosage and Administration (2.2) in the full Prescribing Information]. In Study 1, colitis or diarrhea occurred in 23 (12.6%) patients including Grade 3 or 4 diarrhea in two (1.1%) patients. No patients in Study 1 received systemic corticosteroids or immuno- suppressants for diarrhea or colitis. In the combined safety database, immune-mediated colitis

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