TECENTRIQ (atezolizumab) intravenous injection
|Mechanism of Action||Atezolizumab is a monoclonal antibody that binds to PD-L1 (programmed death- ligand 1) and blocks its interactions with both PD-1 (programmed cell death 1) and B7.1 receptors. This releases the PD-L1/PD-1 mediated inhibition of the immune response, including activation of the anti-tumor immune response without inducing antibody- dependent cellular cytotoxicity.|
|Pharmacodynamics (PD)||Not reported.|
|Pharmacokinetics (PK)||The terminal half-life was 27 days
After 6 to 9 weeks (2 to 3 cycles) of repeated dosing, the systemic accumulation in AUC, Cmax and Cmin were 1.91, 1.46 and 2.75-fold, respectively.
|PK-PD Analysis||Not reported.|
|Population PK||Typical population clearance and volume of distribution at steady state were 0.20 L/day and 6.9 L, respectively.
In a post-hoc analysis, atezolizumab clearance was found to decrease over time, with a mean maximal reduction from baseline value of approximately 17.1% (CV% of 40.6%). However, the decrease in CL was not considered clinically relevant.
| Age (21–89 years), body weight, gender, positive anti-therapeutic antibody (ATA) status, albumin levels, tumor burden, region or race, mild or moderate renal impairment (estimated glomerular filtration rate (eGFR) 30 to 89 mL/min/1.73 m2), mild hepatic impairment (bilirubin ≤ ULN and AST > ULN or bilirubin < 1.0 to 1.5 × ULN and any AST), level of PD-L1 expression, or ECOG status had no clinically significant effect on the systemic exposure of atezolizumab.
The effect of severe renal impairment (eGFR 15 to 29 mL/min/1.73 m2) or moderate or severe hepatic impairment (bilirubin > ULN and AST > ULN or bilirubin ≥1.0 to 1.5 × ULN and any AST) on the pharmacokinetics of atezolizumab is unknown.
|The drug interaction potential of atezolizumab is unknown.|