THE COMBINATION of pembrolizumab and cabozantinib demonstrated antitumor activity in patients with previously treated metastatic renal cell carcinoma and both drugs were tolerable at their approved doses, according to data from a dose-escalation cohort of a phase I study.1
Among eight patients with renal cell carcinoma of any histology, the best objective response was a partial response in two patients and stable disease in four patients; two patients experienced progressive disease. The maximum tolerated dose was identified as pembrolizumab 200 mg every 3 weeks plus oral cabozantinib 60 mg daily.
No dose-limiting toxicities were observed with cabozantinib at 40 mg when used in combination with pembrolizumab in evaluable patients. One patient required a dose reduction from 60 mg of cabozantinib to 40 mg after cycle 5.
Side effects of cabozantinib were as expected. The most common treatment-emergent adverse events of any grade at either cabozantinib dosage were fatigue (75%), diarrhea (62.5%), weight loss (62.5%), and dysgeusia (50%).
Patients in the study were not selected for programmed cell death ligand 1 (PD-L1) expression. No correlation with PD-L1 status and response was seen in tumor samples tested.
Molika E. Keeler, MD
“These data suggest encouraging early efficacy, and we will proceed with a phase II trial,” said lead author Molika E. Keeler, MD, University of Colorado, Aurora, Colorado.
Based on these findings, a 2-stage phase II study, with a planned enrollment of 20 treatment-naive or previously treated patients, was initiated in patients with renal cell carcinoma with either clear cell or non–clear cell histology. The investigators plan to expand the phase II study, depending on responses. ■
DISCLOSURE: Dr. Keeler reported no conflicts of interest.
1. Keeler ME, Kessler ER, Bernard B, et al. Pembrolizumab and cabozantinib in patients with metastatic renal cell carcinoma: Phase I results. 2019 Genitourinary Cancers Symposium. Abstract 600. Presented February 16, 2019.