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A phase 1-2 trial of sitravatinib and nivolumab in clear cell renal cell carcinoma following progression on antiangiogenic therapy.
- Source :
-
Science translational medicine [Sci Transl Med] 2022 Apr 20; Vol. 14 (641), pp. eabm6420. Date of Electronic Publication: 2022 Apr 20. - Publication Year :
- 2022
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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-naïve 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.
Details
- Language :
- English
- ISSN :
- 1946-6242
- Volume :
- 14
- Issue :
- 641
- Database :
- MEDLINE
- Journal :
- Science translational medicine
- Publication Type :
- Academic Journal
- Accession number :
- 35442707
- Full Text :
- https://doi.org/10.1126/scitranslmed.abm6420