Atezolizumab
Atezolizumab, a biologic. Humanised IgG1 mAb with engineered aglycosylated Fc (N297A) targeting PD-L1. Blocks PD-L1 engagement of PD-1 and B7.1… IV half-life 27 d.
Humanised IgG1 mAb with engineered aglycosylated Fc (N297A) targeting PD-L1. Blocks PD-L1 engagement of PD-1 and B7.1, relieving T cell inhibition. Fc aglycosylation eliminates ADCC/CDC so tumour-infiltrating T cells (which also express PD-L1) are not killed. First PD-L1 inhibitor approved.
PK: Stroh 2017 (PMID:27981577), population analysis in 906 patients with metastatic urothelial carcinoma, verbatim "the clearance, volume of distribution, and terminal half-life estimates from population pharmacokinetic (PopPK) analysis of 0.200 L/day, 6.91 L, and 27 days". The 27-day half-life stands as stored; the volume was 7 L, a registry-wide default, and is corrected to the paper's own figure. That 6.91 L is a STEADY-STATE volume — the central volume is roughly half it at 3.01 L (PMID:31753029) — so a one-compartment curve pairing Vss with a terminal half-life is a known approximation. mw corrected from the generic 148000 to 145000: the approval document states "a calculated molecular mass of 145 kDa", lighter than a typical IgG1 because this antibody is non-glycosylated. CAVEATS: clearance falls up to 22% over treatment (PMID:33904970), so a fixed half-life averages over time; disposition is nonlinear in CYNOMOLGUS MONKEY and MOUSE (PMID:26918260) but linear in humans at clinical doses.
Pharmacokinetics
- IV — t½ 27.0 d · F 100% · Vd 6.91 L
Sources: PMID:27981577, PMID:31753029, PMID:33904970