Single-center phase 2 trial of neoadjuvant cabozantinib for locally advanced nonmetastatic clear cell renal cell carcinoma

Cabozantinib is an oral multikinase inhibitor approved for treatment of metastatic renal cell carcinoma (RCC). A phase 2 clinical trial at Emory University (Atlanta, GA) evaluated twelve weeks of neoadjuvant cabozantinib 60 mg once daily for nonmetastatic, locally advanced clear cell RCC, followed by surgical resection. The primary endpoint was objective response rate at 12 weeks. Six of 17 patients (35%) had partial response; the other 11 patients (65%) had stable disease.There were no grade 4 or 5 adverse events related to cabozantinib or surgery. One-year disease-free survival and overall survival were 82.4% (95% CI 54.7-93.9) and 94.1% (65-99.1), respectively. Cabozantinib activated CD8⁺ T cells in the blood, depleted myeoloid populations, and induced immune niches for TCF1⁺ stem-like CD8⁺ T cells. The authors conclude that neoadjuvant cabozantinib was clinically active and safe among patients with locally advanced nonmetastatic clear cell RCC.