on its mechanism of action, IMFINZI can cause fetal harm when administered to a pregnant woman [see USE IN SPECIFIC POPULATIONS (8.1)]. Advise females of reproductive potential to use effective contraception during treatment with IMFINZI, and for at least 3 months following the last dose of IMFINZI.
8.4 Pediatric Use
The safety and effectiveness of IMFINZI have not been established in pediatric patients.
8.5 Geriatric Use
Of the 182 patients treated with IMFINZI, 112 patients were 65 years or older and 34 patients were 75 years or older. The overall response rate in patients 65 years or older was 15.2% (17/112) and was 11.8% (4/34) in patients 75 years or older. Grade 3 or 4 adverse reactions occurred in 38% (42/112) of patients 65 years or older and 35% (12/34) of patients 75 years or older. Study results in patients > 65 years of age and particularly in those > 75 years of age should be viewed with caution given the small number of patients.
10 OVERDOSAGE
There is no information on overdose with IMFINZI.
11 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.
12.2 Pharmacodynamics
The exposure-response relationships for efficacy and safety are unknown.
Cardiac Electrophysiology
Durvalumab is unlikely to prolong the QT/QTc interval.
12.3 Pharmacokinetics
The pharmacokinetics of durvalumab was studied in 1324 patients with doses ranging from 0.1 mg/kg (0.01 times the approved recommended dosage) to 20 mg/kg (2 times the approved recommended dosage) administered once every |
