Atezolizumab, an Anti- @entity4634 Antibody, in XXXX : Long-Term Safety, Clinical Activity, and Immune Correlates From a Phase Ia Study.

@entity4634 @entity1 @entity137 @entity5 @entity1358 @entity72831
PURPOSE: The objective was to determine the safety and clinical activity of atezolizumab (MPDL3280A), a humanized @entity4634 ( @entity4634 ) antibody, in @entity1358 ( @entity1358 ). Exploratory biomarkers were analyzed and associated with outcomes. @entity1 AND METHODS: Seventy @entity1 with metastatic @entity1358 , including clear cell (ccRCC; n = 63) and non-clear cell (ncc; n = 7) histologies, received atezolizumab intravenously every 3 weeks. @entity4634 expression was scored at four diagnostic levels (0/1/2/3) that were based on @entity4634 staining on @entity5 cells and @entity5 -infiltrating immune cells (IC) with the SP142 assay. Primary end points were safety and @entity137 ; secondary end points assessed clinical activity per Response Evaluation Criteria in Solid Tumors version 1.1 and immune-related response criteria. Plasma and tissue were analyzed for potential biomarkers of atezolizumab response. RESULTS: Grade 3 treatment-related and immune-mediated adverse events occurred in 17% and 4% of @entity1 , respectively, and there were no grade 4 or 5 events. Sixty-three @entity1 with ccRCC were evaluable for overall survival (median, 28.9 months; 95% CI, 20.0 months to not reached) and progression-free survival (median, 5.6 months; 95% CI, 3.9 to 8.2 months), and 62 @entity1 were evaluable for objective response rate (ORR; 15%; 95% CI, 7% to 26%). ORR was evaluated on the basis of @entity4634 IC expression ( @entity72831 : n = 33; 18%; 95% CI, 7% to 35%; and IC0: n = 22; 9%; 95% CI, 1% to 29%). The ORR for @entity1 with Fuhrman grade 4 and/or sarcomatoid histology was 22% (n = 18; 95% CI, 6% to 48%). Decreases in circulating plasma markers and acute-phase proteins and an increased baseline effector T-cell-to-regulatory T-cell gene expression ratio correlated with response to atezolizumab. CONCLUSION: Atezolizumab demonstrated a manageable safety profile and promising antitumor activity in @entity1 with metastatic @entity1358 . Correlative studies identified potential predictive and pharmacodynamic biomarkers. These results have guided ongoing studies and combinations with atezolizumab in @entity1358 .
