Atezolizumab plus bevacizumab in non-clear cell renal cell carcinoma (NccRCC) and clear cell renal cell carcinoma with sarcomatoid differentiation (ccRCCsd): Updated results of activity and predictive biomarkers from a phase II study.

Authors

null

Ronan Flippot

Dana-Farber Cancer Institute, Boston, MA

Ronan Flippot , Bradley Alexander McGregor , Abdallah Flaifel , Kathryn P. Gray , Sabina Signoretti , John A. Steinharter , Eliezer Mendel Van Allen , Meghara K. Walsh , Katy Gundy , Xiao X. Wei , Lauren Christine Harshman , Ulka N. Vaishampayan , Toni K. Choueiri , Rana R. McKay

Organizations

Dana-Farber Cancer Institute, Boston, MA, Brigham and Women's Hospital, Boston, MA, Dana-Farber Cancer Institute/Partners Cancer Care, Boston, MA, Dana Farber Cancer Institute, Boston, MA, Wayne State University, Detroit, MI, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA

Research Funding

Pharmaceutical/Biotech Company
Institutional

Background: NccRCC and ccRCCsd are aggressive tumors associated with poor prognosis and response to therapy. Combination strategies co-targeting VEGF signaling and inhibitory immune checkpoints are highly active in clear-cell renal cell carcinoma, but data is lacking in NccRCC and ccRCCsd. We conducted a multicenter, open-label, single arm phase II trial of atezolizumab plus bevacizumab in NccRCC and ccRCCsd. Methods: Patients with NccRCC and ccRCCsd ( > 20% sarcomatoid differentiation), and ECOG performance status of 0-2 were eligible. Prior systemic treatment was allowed with the exception of prior PD-1/PD-L1-directed therapy. Atezolizumab 1200mg and bevacizumab 15mg/kg were administered every 3 weeks until progression, unacceptable toxicity, or patient withdrawal. Primary endpoint was objective response rate (ORR) per RECIST 1.1. Exploratory biomarker analyses included PD-L1 expression on tumor (TC) and immune cells (IC), and spatial analysis of the immune infiltrate. Results: Sixty patients received at least 1 cycle of treatment, among whom 56 were evaluable for response (17 ccRCCsd and 39 NccRCC). ORR was 34% in the overall population, 53% in ccRCCsd and 26% in NccRCC. Median progression-free survival was 8.4 months (95%CI, 6.9-16.5). Baseline tumor tissue was available for 36 patients. TC PD-L1 expression ≥1% was associated with improved ORR (9/14, 64%) compared to patients with PD-L1 expression < 1% (4/20, 20%). Patients with TC PD-L1 expression ≥1% who experienced progressive disease as best response had shorter average distance between tumor cells and nearest neighboring immune cells at baseline. Further analysis of the immune tumor microenvironment on an expanded cohort, including IC PD-L1 expression and correlation with clinical outcomes, is ongoing and will be updated. Conclusions: The combination of atezolizumab plus bevacizumab is active in NccRCC and ccRCCsd. Candidate predictive biomarkers include PD-L1 expression in TC and topological analysis of the immune infiltrate. Clinical trial information: NCT02724878

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Abstract Details

Meeting

2019 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Genitourinary (Nonprostate) Cancer

Track

Genitourinary Cancer—Kidney and Bladder

Sub Track

Kidney Cancer

Clinical Trial Registration Number

NCT02724878

Citation

J Clin Oncol 37, 2019 (suppl; abstr 4583)

DOI

10.1200/JCO.2019.37.15_suppl.4583

Abstract #

4583

Poster Bd #

409

Abstract Disclosures