Atezolizumab, an anti-programmed death-ligand 1 antibody, in metastatic renal cell carcinoma: Long-term safety, clinical activity, and immune correlates from a phase Ia study

David F. McDermott*, Jeffrey A. Sosman, Mario Sznol, Christophe Massard, Michael S. Gordon, Omid Hamid, John D. Powderly, Jeffrey R. Infante, Marcella Fassò, Yan V. Wang, Wei Zou, Priti S. Hegde, Gregg D. Fine, Thomas Powles

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

357 Scopus citations

Abstract

Purpose: The objective was to determine the safety and clinical activity of atezolizumab (MPDL3280A), a humanized programmed death-ligand 1 (PD-L1) antibody, in renal cell carcinoma (RCC). Exploratory biomarkers were analyzed and associated with outcomes. Patients and Methods: Seventy patients with metastatic RCC, including clear cell (ccRCC; n = 63) and non-clear cell (ncc; n = 7) histologies, received atezolizumab intravenously every 3 weeks. PD-L1 expression was scored at four diagnostic levels (0/1/2/3) that were based on PD-L1 staining on tumor cells and tumorinfiltrating immune cells (IC) with the SP142 assay. Primary end points were safety and toxicity; 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: Grade3 treatment-related and immune-mediated adverse events occurred in 17% and4%ofpatients, respectively, and there were no grade 4 or 5 events. Sixty-three patients 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 patients were evaluable for objective response rate (ORR; 15%; 95% CI, 7% to 26%). ORR was evaluated on the basis of PD-L1 IC expression (IC1/2/3:n=33; 18%; 95% CI,7%to35%; and IC0:n= 22; 9%; 95% CI,1% to29%). The ORR for patients 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 patients with metastatic RCC. Correlative studies identified potential predictive and pharmacodynamic biomarkers. These results have guided ongoing studies and combinations with atezolizumab in RCC.

Original languageEnglish (US)
Pages (from-to)833-842
Number of pages10
JournalJournal of Clinical Oncology
Volume34
Issue number8
DOIs
StatePublished - Mar 10 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Atezolizumab, an anti-programmed death-ligand 1 antibody, in metastatic renal cell carcinoma: Long-term safety, clinical activity, and immune correlates from a phase Ia study'. Together they form a unique fingerprint.

Cite this