For: Urothelial Carcinoma, Non-Small Cell Lung Cancer
Imfinzi (durvalumab) is an anti-PD-L1 (programmed death ligand-1) human monoclonal antibody for the treatment of patients with metastatic urothelial carcinoma and for the treatment of patients with unresectable non-small cell lung cancer that has not progressed after chemoradiation. DURVALUMAB
IMFINZI- durvalumab injection, solution
AstraZeneca Pharmaceuticals LP
1 INDICATIONS AND USAGE
IMFINZI is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who:
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have disease progression during or following platinum-containing chemotherapy.
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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)].
2 DOSAGE AND ADMINISTRATION
2.1 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.
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.
DESCRIPTION
Durvalumab is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that blocks the interaction of programmed cell death ligand 1 (PD-L1) with the PD-1 and CD80 (B7.1) molecules. Durvalumab is produced by recombinant DNA technology in Chinese Hamster Ovary (CHO) cell suspension culture.
IMFINZI (durvalumab) Injection for intravenous use is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow solution, free from visible particles.
Each 500 mg vial of IMFINZI contains 500 mg of durvalumab in 10 mL solution. Each mL contains durvalumab, 50 mg, L-histidine (2 mg), L-histidine hydrochloride monohydrate (2.7 mg), α,α-trehalose dihydrate (104 mg), Polysorbate 80 (0.2 mg), and Water for Injection, USP.
Each 120 mg vial of IMFINZI contains 120 mg of durvalumab in 2.4 mL solution. Each mL contains durvalumab, 50 mg, L-histidine (2 mg), L-histidine hydrochloride monohydrate (2.7 mg), α,α-trehalose dihydrate (104 mg), Polysorbate 80 (0.2 mg), and Water for Injection, USP.
12 CLINICAL PHARMACOLOGY
12.1 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 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.
