Discussion
tumor, RCC
TUMOR, BONE METASTASES, RCC
We conducted this phase I/II study of pembrolizumab and cabozantinib beginning in 2017, prior to the FDA approvals of combination CPI-TKI therapies including pembrolizumab and axitinib in 2019, and nivolumab and cabozantinib and pembrolizumab and lenvatinib in 2021. In our study, the primary endpoint of ORR for all patients treated at the RP2D was met, with ORR 65.8%. The ORR was 73.3% among 1 L patients and 56% among 2 L patients. These results are better than historical results from cabozantinib alone (33% in 1 L and 21% in 2 L+; refs. The safety profile of pembrolizumab plus cabozantinib was manageable and generally consistent with AEs reported with other CPI-TKI combinations. As with the phase I nivolumab and cabozantinib study (Our exploratory analyses included PD-L1 tumor testing in all patients with archival tissue and bone turnover markers in patients with bone metastases at baseline. In contrast to previously seen responses to pembrolizumab in advanced RCC with positive PD-L1 expression (