Single-center randomized phase 1 trial of first-line cabozantinib and nivolumab with or without CMB588 for metastatic renal cell carcinoma

CBM588 is a bifidogenic live bacterial product. A pilot randomized phase 1 trial at City of Hope Comprehensive Cancer Center (Duarte, CA) evaluated cabozantinib and nivolumab with or without CBM588 as first-line treatment for metastatic renal cell carcinoma (mRCC). Twenty-nine mRCC patients were randomized 2:1 to cabozantinib plus nivolumab plus CBM588 (n=19) or cabozantinib plus nivolumab alone (n=10). The primary endpoint was a change in relative abundance in Bifidobacterium spp. in stool samples at 13 weeks. This endpoint was not met since addition of CBM588 did not result in a difference in the relative abundance of Bifidobacterium spp. However, the objective response rate was significantly higher in the CMB588 arm compared to the control arm (74% versus 20%; p=0.01). Progression-free survival rate at 6 months was 84% versus 60%. There was no significant difference in toxicity profile between the arms. The authors conclude that these results provide a preliminary signal of improved clinical activity with CBM588 in treatment-naïve patients with mRCC receiving cabozantinab and nivolumab.