Atezolizumab

Target and mechanism. Atezolizumab blocks the interaction of programmed death-ligand 1 (PD-L1) with programmed cell death 1 (PD-1) and CD80 receptors (B7-1Rs).

Current approvals. Atezolizumab is approved for non-small cell lung cancer,[1-5] small-cell lung cancer,[6] hepatocellular carcinoma,[7] melanoma,[8] and alveolar soft part sarcoma.[9]

Supporting study. Atezolizumab was evaluated in a phase IIa, multibasket, MyPathway study. The preplanned primary end point was objective response rate in patients with TMB-H (≥16 mut/Mb) tumors by FoundationOne TMB testing.[10]

Study population. This study included 120 patients with advanced solid tumors with TMB ≥10 mut/Mb by any Clinical Laboratory Improvement Amendments (CLIA)-certified assay. Among patients with local or central FoundationOne TMB testing results, 42 had TMB ≥16 mut/Mb tumors, comprising the primary efficacy population, and 49 had TMB ≥10 and <16 mut/Mb tumors, of whom 48 were efficacy evaluable.[10]

Efficacy. In the primary analysis population of 42 patients with TMB ≥16 mut/Mb tumors, the confirmed objective response rate was 38.1% (95% confidence interval [CI], 23.6%–54.4%) and the disease-control rate (the best response of complete response, partial response, or stable disease >4 months) was 61.9% (95% CI, 45.6%–76.4%), with a median follow-up of 9.9 months.[10][Level of evidence C3]