A phase 1 trial evaluated the effect of CBM588, a live bacterial supplement, on the gut microbiome and clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) receiving cabozantinib and nivolumab. Thirty participants were randomized in a 2:1 ratio to receive the combination therapy with or without CBM588. Stool samples were collected to analyze the gut microbiome at baseline and week 13. The primary endpoint was the change in Bifidobacterium spp. abundance, which did not show significant differences between the groups. However, the addition of CBM588 was associated with a higher objective response rate (ORR) and progression-free survival (PFS) compared to the control group. The ORR was 74% in the CBM588 group versus 20% in the control group. PFS at 6 months was 84% in the experimental group versus 60% in the control group. No significant differences in toxicity were observed between the groups. The study suggests that CBM588 may improve clinical outcomes in mRCC patients receiving cabozantinib and nivolumab. However, further research is needed to confirm these findings and understand the underlying mechanisms. The study highlights the potential of microbiome modulation as a strategy to enhance immunotherapy efficacy in cancer treatment.A phase 1 trial evaluated the effect of CBM588, a live bacterial supplement, on the gut microbiome and clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) receiving cabozantinib and nivolumab. Thirty participants were randomized in a 2:1 ratio to receive the combination therapy with or without CBM588. Stool samples were collected to analyze the gut microbiome at baseline and week 13. The primary endpoint was the change in Bifidobacterium spp. abundance, which did not show significant differences between the groups. However, the addition of CBM588 was associated with a higher objective response rate (ORR) and progression-free survival (PFS) compared to the control group. The ORR was 74% in the CBM588 group versus 20% in the control group. PFS at 6 months was 84% in the experimental group versus 60% in the control group. No significant differences in toxicity were observed between the groups. The study suggests that CBM588 may improve clinical outcomes in mRCC patients receiving cabozantinib and nivolumab. However, further research is needed to confirm these findings and understand the underlying mechanisms. The study highlights the potential of microbiome modulation as a strategy to enhance immunotherapy efficacy in cancer treatment.