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J Clin Oncol. 2016 Mar 10;34(8):833-42. doi: 10.1200/JCO.2015.63.7421. Epub 2016 Jan 11.

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.

Author information

1
David F. McDermott, Beth Israel Deaconess Medical Center, Boston, MA; Jeffrey A. Sosman, Vanderbilt University School of Medicine; Jeffrey R. Infante, Sarah Cannon Research Institute, Nashville, TN; Mario Sznol, Yale Cancer Center, New Haven, CT; Christophe Massard, Gustave Roussy, Villejuif Cedex, France; Michael S. Gordon, Pinnacle Oncology Hematology, Scottsdale, AZ; Omid Hamid, Angeles Clinic and Research Institute, Santa Monica; Marcella Fassò, Yan V. Wang, Wei Zou, Priti S. Hedge, and Gregg D. Fine, Genentech, South San Francisco, CA; John D. Powderly, Carolina BioOncology Institute, Huntersville, NC; and Thomas Powles, Barts Cancer Institute Centre for Experimental Cancer Medicine and the Royal Free National Health Service Trust, Queen Mary University of London, London, United Kingdom. dmcdermo@bidmc.harvard.edu.
2
David F. McDermott, Beth Israel Deaconess Medical Center, Boston, MA; Jeffrey A. Sosman, Vanderbilt University School of Medicine; Jeffrey R. Infante, Sarah Cannon Research Institute, Nashville, TN; Mario Sznol, Yale Cancer Center, New Haven, CT; Christophe Massard, Gustave Roussy, Villejuif Cedex, France; Michael S. Gordon, Pinnacle Oncology Hematology, Scottsdale, AZ; Omid Hamid, Angeles Clinic and Research Institute, Santa Monica; Marcella Fassò, Yan V. Wang, Wei Zou, Priti S. Hedge, and Gregg D. Fine, Genentech, South San Francisco, CA; John D. Powderly, Carolina BioOncology Institute, Huntersville, NC; and Thomas Powles, Barts Cancer Institute Centre for Experimental Cancer Medicine and the Royal Free National Health Service Trust, Queen Mary University of London, London, United Kingdom.

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 tumor-infiltrating 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:

Grade 3 treatment-related and immune-mediated adverse events occurred in 17% and 4% of patients, 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% to 35%; and IC0: n = 22; 9%; 95% CI, 1% to 29%). 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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01375842.

PMID:
26755520
DOI:
10.1200/JCO.2015.63.7421
[Indexed for MEDLINE]

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