@article{2a23b11a1c714c2f9f76b4d899980ae4,
title = "A phase 1-2 trial of sitravatinib and nivolumab in clear cell renal cell carcinoma following progression on antiangiogenic therapy",
abstract = "The accumulation of immune-suppressive myeloid cells is a critical determinant of resistance to anti–programmed death-1 (PD-1) therapy in advanced clear cell renal cell carcinoma (ccRCC). In preclinical models, the tyrosine kinase inhibitor sitravatinib enhanced responses to anti–PD-1 therapy by modulating immune-suppressive myeloid cells. We conducted a phase 1-2 trial to choose an optimal sitravatinib dose combined with a fixed dose of nivolumab in 42 immunotherapy-na{\"i}ve patients with ccRCC refractory to prior antiangiogenic therapies. The combination demonstrated no unexpected toxicities and achieved an objective response rate of 35.7% and a median progression-free survival of 11.7 months, with 80.1% of patients alive after a median follow-up of 18.7 months. Baseline peripheral blood neutrophil-to-lymphocyte ratio correlated with response to sitravatinib and nivolumab. Patients with liver metastases showed durable responses comparable to patients without liver metastases. In addition, correlative studies demonstrated reduction of immune-suppressive myeloid cells in the periphery and tumor microenvironment following sitravatinib treatment. This study provides a rationally designed combinatorial strategy to improve outcomes of anti–PD-1 therapy in advanced ccRCC.",
author = "Pavlos Msaouel and Sangeeta Goswami and Thall, {Peter F.} and Xuemei Wang and Ying Yuan and Eric Jonasch and Jianjun Gao and Campbell, {Matthew T.} and Shah, {Amishi Yogesh} and Corn, {Paul Gettys} and Tam, {Alda L.} and Kamran Ahrar and Priya Rao and Kanishka Sircar and Lorenzo Cohen and Sreyashi Basu and Fei Duan and Sonali Jindal and Yuwei Zhang and Hong Chen and Yadav, {Shalini S.} and Ronald Shazer and Hirak Der-Torossian and Allison, {James P.} and Padmanee Sharma and Tannir, {Nizar M.}",
note = "Funding Information: This investigator-initiated trial was supported in part by the Cancer Center Support Grant to The University of Texas MD Anderson Cancer Center (grant number P30 CA016672) from the National Cancer Institute of the National Institutes of Health, by Mirati Therapeutics, and by the Gateway for Cancer Research award G-17-600 to P.M. P.M. is supported by a Career Development Award from the American Society of Clinical Oncology, the MD Anderson Khalifa Scholar Award, and the MD Anderson Physician-Scientist Award and is an Andrew Sabin Family Foundation Fellow. S.G. is supported by the K12 Calabresi Scholars Award, the Emerson Collective Award, the MD Anderson Khalifa Scholar Award, and the MD Anderson Physician-Scientist Award and is an Andrew Sabin Family Foundation Fellow. Publisher Copyright: Copyright {\textcopyright} 2022 The Authors, some rights reserved.",
year = "2022",
month = apr,
day = "20",
doi = "10.1126/scitranslmed.abm6420",
language = "English (US)",
volume = "14",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "641",
}